Response rates to chemotherapy remain highly variable in breast cancer patients. We set out to identify genes associated with chemotherapy resistance. We analyzed what is currently the largest ...single-institute set of gene expression profiles derived from breast cancers prior to a single neoadjuvant chemotherapy regimen (dose-dense doxorubicin and cyclophosphamide). We collected, gene expression-profiled, and analyzed 178 HER2-negative breast tumor biopsies (“NKI dataset”). We employed a recently developed approach for detecting imbalanced differential signal (DIDS) to identify markers of resistance to treatment. In contrast to traditional methods, DIDS is able to identify markers that show aberrant expression in only a small subgroup of the non-responder samples. We found a number of markers of resistance to anthracycline-based chemotherapy. We validated our findings in three external datasets, totaling 456 HER2-negative samples. Since these external sets included patients who received differing treatment regimens, the validated markers represent markers of general chemotherapy resistance. There was a highly significant overlap in the markers identified in the NKI dataset and the other three datasets. Five resistance markers, SERPINA6, BEX1, AGTR1, SLC26A3, and LAPTM4B, were identified in three of the four datasets (
p
value overlap < 1 × 10
−6
). These five genes identified resistant tumors that could not have been identified by merely taking ER status or proliferation into account. The identification of these genes might lead to a better understanding of the mechanisms involved in (clinically) observed chemotherapy resistance and could possibly assist in the recognition of breast cancers in which chemotherapy does not contribute to response or survival.
Purpose
Breast cancer (BC) patients undergoing FDG-PET/CT scans for neoadjuvant chemotherapy (NAC) may have additional non-BC related findings. The aim of this study is to describe the clinical ...implications of these findings.
Methods
We included BC patients who underwent an FDG-PET/CT scan in our institute between 2011–2020 prior to NAC. We focused on patients with an additional non-BC related finding (i.e. BC metastases were excluded) for which diagnostic work-up was performed. Information about the diagnostic work-up and the clinical consequences was retrospectively gathered. A revision of all FDG-PET/CT scans was conducted by an independent physician to assess the suspicion level of the additional findings.
Results
Of the 1337 patients who underwent FDG-PET/CT, 202 patients (15%) had an non-BC related additional finding for which diagnostic work-up was conducted, resulting in 318 examinations during the first year. The non-BC related findings were mostly detected in the endocrine region (26%), gastro-intestinal region (16%), or the lungs (15%). Seventeen patients (17/202: 8%, 17/1337: 1.3%) had a second primary malignancy. Only 8 patients (8/202: 4%, 8/1337: 0.6%) had a finding that was considered more prognosis-determining than their BC disease. When revising all FDG-PET/CT scans, 57 (202/57: 28%) of the patients had an additional finding categorized as low suspicious, suggesting no indication for diagnostic work-up.
Conclusion
FDG-PET/CT scans used for dissemination imaging in BC patients detect a high number of non-BC related additional findings, often clinically irrelevant and causing a large amount of unnecessary work-up. However, in 8% of the patients undergoing diagnostic work-up for an additional finding, a second primary malignancy was detected, warranting diagnostic attention in selected patients.
There is an unmet clinical need for an accurate, rapid and reliable tool for margin assessment during breast-conserving surgeries. Ultrasound offers the potential for a rapid, reproducible, and ...non-invasive method to assess margins. However, it is challenged by certain drawbacks, including a low signal-to-noise ratio, artifacts, and the need for experience with the acquirement and interpretation of images. A possible solution might be computer-aided ultrasound evaluation. In this study, we have developed new ensemble approaches for automated breast tumor segmentation. The ensemble approaches to predict positive and close margins (distance from tumor to margin ≤ 2.0 mm) in the ultrasound images were based on 8 pre-trained deep neural networks. The best optimum ensemble approach for segmentation attained a median Dice score of 0.88 on our data set. Furthermore, utilizing the segmentation results we were able to achieve a sensitivity of 96% and a specificity of 76% for predicting a close margin when compared to histology results. The promising results demonstrate the capability of AI-based ultrasound imaging as an intraoperative surgical margin assessment tool during breast-conserving surgery.
Purpose
Oncoplastic surgery (OPS) after breast conserving surgery is preferably performed during the same operation. Offering delayed OPS instead of mastectomy to patients with a high risk of ...tumor-positive margins allows breast conservation with the option of margin re-excision during OPS, without having to dismantle the reconstruction. We aimed to evaluate surgical outcomes after immediate and delayed OPS.
Methods
We included early-stage breast cancer patients who underwent OPS at the Netherlands Cancer Institute between 2016 and 2019. Patients were selected for delayed OPS after multidisciplinary consultation if the risk of tumor-positive margins with immediate OPS was considered significant (> 30%). Groups were compared on baseline characteristics and short-term surgical outcomes.
Results
Of 242 patients with 251 OPS, 130 (52%) OPS had neoadjuvant chemotherapy. Immediate OPS was performed in 176 (70%) cases and delayed OPS in 76 (30%). Selection for delayed OPS was associated with tumor size (OR 1.03, 95% CI 1.01–1.04), ILC (OR 2.61, 95% CI 1.10–6.20), DCIS (OR 3.45, 95% CI 1.42–8.34) and bra size (OR 0.76, 95% CI 0.62–0.94). Delayed and immediate OPS differed in tissue weight (54 vs. 67 g,
p
= 0.034), tissue replacement (51% vs. 26%,
p
< .001) and tumor-positive margins (66% vs. 18%,
p
< .001). Re-excision was performed in 48 (63%) delayed OPS and in 11 (6%) immediate OPS. Groups did not differ in complications (21% vs. 18%,
p
= 0.333). Breast conservation after immediate and delayed OPS was 98% and 93%, respectively.
Conclusion
Performing delayed OPS in selected cases facilitated simultaneous margin re-excision without increasing complications, and resulted in an excellent breast conservation rate.
Background
Despite increasingly effective curative breast-conserving treatment (BCT) regimens for primary breast cancer, patients remain at risk for an ipsilateral breast tumor recurrence (IBTR). ...With increasing interest for repeat BCT in selected patients with IBTR, a reliable assessment of the size of IBTR is important for surgical planning.
Aim
The primary aim of this study is to establish the performance in size estimation of XMG, US, and breast MRI in patients with IBTR. The secondary aim is to compare the detection of multifocality and contralateral lesions between XMG and MRI.
Patients and methods
The sizes of IBTR on mammography (XMG), ultrasound (US), and magnetic resonance imaging (MRI) in 159 patients were compared to the sizes at final histopathology. The accuracy of the size estimates was addressed using Pearson’s coefficient and Bland–Altman plots. Secondary outcomes were the detection of multifocality and contralateral lesions between XMG and MRI.
Results
Both XMG and US significantly underestimated the tumor size by 3.5 and 4.8 mm, respectively, while MRI provided accurate tumor size estimation with a mean underestimation of 1.1 mm. The sensitivity for the detection of multifocality was significantly higher for MRI compared to XMG (25.5% vs. 5.5%). A contralateral malignancy was found in 4.4% of patients, and in 1.9%, it was detected by MRI only.
Conclusion
The addition of breast MRI to XMG and US in the preoperative workup of IBTR allows for more accurate size estimation. MRI provides a higher sensitivity for the detection of multifocality compared to XMG.
Purpose
Neoadjuvant systemic therapy (NST) is increasingly used in breast cancer patients and depending on subtype, 10–89% of patients will attain pathologic complete response (pCR). In patients with ...pCR, risk of local recurrence (LR) after breast conserving therapy is low. Although adjuvant radiotherapy after breast conserving surgery (BCS) reduces LR further in these patients, it may not contribute to overall survival. However, radiotherapy may cause early and late toxicity. The aim of this study is to show that omission of adjuvant radiotherapy in patients with a pCR after NST will result in acceptable low LR rates and good quality of life.
Methods
The DESCARTES study is a prospective, multicenter, single arm study. Radiotherapy will be omitted in cT1-2N0 patients (all subtypes) who achieve a pCR of the breast and lymph nodes after NST followed by BCS plus sentinel node procedure. A pCR is defined as ypT0N0 (i.e. no residual tumor cells detected). Primary endpoint is the 5-year LR rate, which is expected to be 4% and deemed acceptable if less than 6%. In total, 595 patients are needed to achieve a power of 80% (one-side alpha of 0.05). Secondary outcomes include quality of life, Cancer Worry Scale, disease specific and overall survival. Projected accrual is five years.
Conclusion
This study bridges the knowledge gap regarding LR rates when adjuvant radiotherapy is omitted in cT1-2N0 patients achieving pCR after NST. If the results are positive, radiotherapy may be safely omitted in selected breast cancer patients with a pCR after NST.
Trial registration: This study is registered at ClinicalTrials.gov on June 13th 2022 (NCT05416164). Protocol version 5.1 (15-03-2022).
Introduction: Some aspects of the treatment protocol for breast cancer during pregnancy (PrBC) have not been thoroughly studied. This study provides clarity regarding the safety of the use of ...125I-seeds as a localization technique for breast-conserving surgery in patients with PrBC. Methods: To calculate the exposure to the fetus of one 125I-seed implanted in a breast tumor, we developed a model accounting for the decaying 125I-source, time to surgery, and the declining distance between the 125I-seed and the fetus. The primary outcome was the maximum cumulative fetal dose of radiation at consecutive gestational ages (GA). Results: The cumulative fetal dose remains below 1 mSv if a single 125I-seed is implanted at a GA of 26 weeks. After a GA of 26 weeks, the fetal dose can be at a maximum of 11.6 mSv. If surgery takes place within two weeks of implantation from a GA of 26 weeks, and one week above a GA of 32 weeks, the dose remains below 1 mSv. Conclusion: The use of 125I-seeds is safe in PrBC. The maximum fetal exposure remains well below the threshold of 100 mSv, and therefore, does not lead to an increased risk of fetal tissue damage. Still, we propose keeping the fetal dose as low as possible, preferably below 1 mSv.
This study aims to evaluate several defined specimen parameters that would allow to determine the surgical accuracy of breast-conserving surgeries (BCS) in a representative population of patients. ...These specimen parameters could be used to compare surgical accuracy when using novel technologies for intra-operative BCS guidance in the future. Different specimen parameters were determined among 100 BCS patients, including the ratio of specimen volume to tumor volume (resection ratio) with different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm). Furthermore, the tumor eccentricity maximum tumor-margin distance - minimum tumor-margin distance and the relative tumor eccentricity tumor eccentricity ÷ pathological tumor diameter were determined. Different patient subgroups were compared using Wilcoxon rank sum tests. When using a surgical margin width of 0 mm, 1 mm, 2 mm, and 10 mm, on average, 19.16 (IQR 44.36), 9.94 (IQR 18.09), 6.06 (IQR 9.69) and 1.35 (IQR 1.78) times the ideal resection volume was excised, respectively. The median tumor eccentricity among the entire patient population was 11.29 mm (SD = 3.99) and the median relative tumor eccentricity was 0.66 (SD = 2.22). Resection ratios based on different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm) and the (relative) tumor eccentricity could be valuable outcome measures to evaluate the surgical accuracy of novel technologies for intra-operative BCS guidance.
Purpose
The presence of extensive ductal carcinoma in situ (DCIS) adjacent to HER2-positive invasive breast cancer (IBC) is often a contra-indication for breast-conserving surgery, even in case of ...excellent treatment response of the invasive component. Data on the response of DCIS to neoadjuvant systemic treatment (NST) are limited. Therefore, we estimated the response of adjacent DCIS to NST-containing HER2-blockade in HER2-positive breast cancer patients and assessed the association of clinicopathological and radiological factors with response.
Methods
Pre-NST biopsies were examined to determine presence of DCIS in all women with HER2-positive IBC treated with trastuzumab-containing NST ± pertuzumab between 2004 and 2017 in a comprehensive cancer center. When present, multiple DCIS factors, including grade, calcifications, necrosis, hormone receptor, and Ki-67 expression, were scored. Associations of clinicopathological and radiological factors with complete response were assessed using logistic regression models.
Results
Adjacent DCIS, observed in 138/316 patients with HER2-positive IBC, was eradicated after NST in 46% of patients. Absence of calcifications suspicious for malignancy on pre-NST mammography (odds ratio (OR) 3.75; 95% confidence interval (95% CI) 1.72–8.17), treatment with dual HER2-blockade (OR 2.36; 95% CI 1.17–4.75), a (near) complete response on MRI (OR 3.55; 95% CI 1.31–9.64), and absence of calcifications (OR 3.19; 95% CI 1.34–7.60) and Ki-67 > 20% in DCIS (OR 2.74; 95% CI 1.09–6.89) on pre-NST biopsy were significantly associated with DCIS response.
Conclusions
As DCIS can respond to NST containing HER2-blockade, the presence of extensive DCIS in HER2-positive breast cancer before NST should not always indicate a mastectomy. The predictive factors we found could be helpful when considering breast-conserving surgery in these patients.
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