Respiratory complex I regulates dendritic cell maturation in explant model of human tumor immune microenvironment.

BACKGROUND: Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level. METHODS: Here we establish a patient-derived explant culture (PDEC) model of breast cancer, which retains the immune contexture of the primary tumor, recapitulating cytokine profiles and CD8+T cell cytotoxic activity. RESULTS: We explored the immunomodulatory action of a synthetic lethal BCL2 inhibitor venetoclax+metformin drug combination ex vivo, discovering metformin cannot overcome the lymphocyte-depleting action of venetoclax. Instead, metformin promotes dendritic cell maturation through inhibition of mitochondrial complex I, increasing their capacity to co-stimulate CD4+T cells and thus facilitating antitumor immunity. CONCLUSIONS: Our results establish PDECs as a feasible model to identify immunomodulatory functions of anticancer drugs in the context of patient-specific TIME.

Vacuum-assisted excision of small breast cancers under ultrasound guidance.

PURPOSE: The purpose of this study was to evaluate if it is possible to completely remove small breast cancer tumours with vacuum-assisted excision (VAE) under ultrasound guidance. METHODS: Women ≥ 50 years old with a biopsy proven invasive cancer ≤ 10 mm were selected between October 2021 and November 2021 based on referrals and enrolled in this prospective study. The patients underwent VAE within six weeks following biopsy to remove the tumour. After the tumour was excised and the biopsy cavities margins were shaved, a radioactive seed was inserted into the biopsy cavity. The VAE excision cavity and surrounding tissue were surgically excised. Preliminary VAE results were evaluated after ten patients. For the study to proceed at least 80 % of the breast cancer tumours had to be completely removed by VAE. RESULTS: The tumours median size in mammography was 8.5 mm (6-9 mm) and in ultrasound 6.5 mm (4-9 mm). The shape of the lesion was round in three (30 %), oval in two (20 %) and irregular in five (50 %) patients. None of the tumours were completely removed in the first VAE specimen, meaning that there was invasive cancer or ductal carcinoma in situ (DCIS) in the "shaved margins" and/or the surgical specimen. In five (50 %) cases, the surgical specimen was free of invasive cancer and DCIS. CONCLUSIONS: None of the small invasive breast cancers were completely excised with VAE under ultrasound guidance, therefore it is not a reliable method to remove small breast cancers.

Ultrasonic scissors decrease postoperative bleeding complications in mastectomy: A retrospective multicenter cohort study on 728 patients.

INTRODUCTION: The aim of this study was to evaluate the rate of postoperative bleeding complications (primary outcome) and any other surgical complications (secondary outcome) in mastectomy between two surgical instruments, ultrasonic SonoSurg® scissors (US) and traditional electrocautery (EC). MATERIALS AND METHODS: In total 728 patients undergoing mastectomy in two adjacent university hospitals were retrospectively evaluated in terms of postoperative bleeding episodes, surgical site infections, skin flap necrosis, and any reoperations for 30 postoperative days. A propensity score matching was performed to acquire balanced groups. Patients consuming medications affecting hemostasis were excluded from the study. A multivariable logistic regression analysis was conducted to define the odds ratio (OR) for each complication separately. A cost analysis was performed. RESULTS: The rate of postoperative bleeding complications was significantly lower in patients operated with US (0.3% vs 11.5%, OR 0.020, 95% CI 0.034-0.14) when compared to EC. The rate of surgical site infections (OR 0.65, 95% CI 0.35-1.23) was similar with both instruments, but there were less skin flap necroses (OR 0.35, 95% CI 0.13-0.98) in US group. For any reoperation, the OR for US was 0.13 (95% CI 0.046-0.39), mainly due to the lower number of acute bleeding complications. Even though the US instrument is more expensive than EC, the total cost of the treatment is lower in patients operated with US (3419 vs. 3475 euro). CONCLUSIONS: US seems to be associated with a lower risk of bleeding complications in mastectomy.

Axillary surgery after neoadjuvant therapy in initially node-positive breast cancer: international EUBREAST survey.

BACKGROUND: There is no consensus on axillary management after neoadjuvant therapy (NAT) in patients with clinically node-positive (cN+) breast cancer. To investigate current clinical practice, an international survey was conducted among breast surgeons and radiation oncologists. The aim of the first part of the survey was to provide a snapshot of international discrepancies regarding axillary surgery in this context. METHODS: The European Breast Cancer Research Association of Surgical Trialists (EUBREAST) developed a web-based survey containing 39 questions describing clinical scenarios in the setting of axillary management in patients with cN1 disease converting to ycN0 after NAT. The survey was then distributed to breast surgeons and radiation oncologists via 14 breast cancer societies between April and October 2021. RESULTS: Responses from 349 physicians in 45 countries were recorded. The most common post-NAT axillary surgery in patients with cN1 disease converting to ycN0 was targeted axillary dissection (54.2 per cent), followed by sentinel lymph node biopsy (SLNB) alone (20.9 per cent), level 1-2 axillary lymph node dissection (ALND) (18.4 per cent), level 1-3 ALND (4 per cent), and targeted lymph node biopsy (2.5 per cent). For SLNB alone, dual tracers were most commonly used (62.3 per cent). Management varied widely in patients with ambiguous axillary status before initiation of treatment or a residual metastatic burden in the axilla after NAT. In patients with ycN+ tumours, ALND was the preferred surgical approach for 66.8 per cent of respondents. CONCLUSION: These results highlight the wide heterogeneity in surgical approaches to the axilla after NAT. To standardize the guidelines, further data from clinical research are urgently needed, which underlines the importance of the ongoing AXSANA (EUBREAST-3) study.

Comparison of vacuum-assisted excision (VAE) and breast lesion excision system (BLES) in the treatment of intraductal papillomas.

PURPOSE: This study aims to compare the feasibility of VAE and BLES in the treatment of intraductal papillomas. MATERIAL AND METHODS: Patients with a suspected intraductal papilloma who underwent a BLES or a VAE procedure were included in this retrospective study. The BLES procedures were performed between November 2011 and June 2016 and the VAE procedures between May 2018 and September 2020 at the Department of Radiology of Helsinki University Hospital (HUH). The procedures were performed with an intent of complete removal of the lesions. RESULTS: In total, 72 patients underwent 78 BLES procedures and 95 patients underwent 99 VAE procedures. Altogether 52 (60%) papillomas with or without atypia were completely removed with VAE, whereas 24 (46%) were completely removed with BLES, p = 0.115. The median radiological size of the high-risk lesions completely removed with BLES was 6 mm (4-12 mm), whereas with VAE it was 8 mm (3-22 mm), p = 0.016. Surgery was omitted in 90 (94.7%) non-malignant breast lesions treated with VAE and in 66 (90.4%) treated with BLES, p = 0.368. CONCLUSION: Both VAE and BLES were feasible in the treatment of intraductal papillomas. In most non-malignant lesions surgery was avoided, but VAE was feasible in larger lesions than BLES. However, follow-up ultrasound was needed more often after VAE. The histopathologic assessment is more reliable after BLES, as the lesion is removed as a single sample.

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

Resection margins and local recurrences of impalpable breast cancer: Comparison between radioguided occult lesion localization (ROLL) and radioactive seed localization (RSL).

OBJECTIVES: The aim of this retrospective study is to compare surgical margins, reoperation rates and local recurrences after breast conserving surgery (BCS) using radioguided occult lesion localization (ROLL) or radioactive seed localization (RSL). MATERIALS AND METHODS: We reviewed 744 consecutive patients with impalpable primary invasive breast cancer who underwent BCS at Helsinki University Hospital between 2010 and 2012. ROLL was used in our unit until October 31st, 2011; from November 1st we changed localization method to RSL. RESULTS: 318 patients underwent ROLL and 426 RSL. Patients in the RSL group had more often multifocal (p = 0.013) tumours. No statistically significant differences were found regarding tumour size, specimen weight, histology or grade of tumours or lymph node status. 42 (5.6%) patients were reoperated because of insufficient margins, 13 (4.1%) in the ROLL group and 29 (6.8%) in the RSL group. The reoperation rate was not different between the groups either in the univariable analysis (p = 0.112) or in the multivariable binary logistic regression analysis (p = 0.204). Risk factors for reoperations were multifocality of the tumour (p < 0.001), extensive intraductal component (p < 0.001), larger tumour size (p = 0.011), and smaller specimen weight (p = 0.014). The median follow-up time in the ROLL group was 81 (8-94) months and 64 (3-73) months in the RSL group. The five-year local recurrence-free survival (LRFS) estimates for ROLL and RSL groups were 98.0% and 99.4%, respectively (log-rank test, p = 0.323). CONCLUSION: Reoperation rates and LRFS were comparable for ROLL and RSL in patients with impalpable breast cancer treated with BCS.

Resection margins and local recurrences in breast cancer: Comparison between conventional and oncoplastic breast conserving surgery.

BACKGROUND: This retrospective cohort study aims to compare surgical margins, reoperations and local recurrences after conventional or oncoplastic breast conservation surgery (BCS). Furthermore, we aim to investigate differences between various oncoplastic techniques. MATERIAL AND METHODS: We reviewed 1800 consecutive patients with primary invasive breast cancer (N = 1707) or ductal carcinoma in situ (N = 93) who underwent BCS at Helsinki University Hospital between 2010 and 2012. RESULTS: Conventional BCS was performed in 1189 (66.1%) patients, oncoplastic BCS in 611 (33.9%). Various oncoplastic techniques were used. Patients with oncoplastic BCS had more often multifocal (p < 0.001), larger (p < 0.001), palpable tumours (p < 0.001) with larger resection specimens (p < 0.001). The amount of resected tissue varied substantially depending on the oncoplastic technique. Patients treated with oncoplastic BCS were younger (p < 0.001) and their tumours were more aggressive according to histological grade (p < 0.001), T-stage (p < 0.001), Ki-67 (p < 0.001) and lymph node status (p < 0.001). There was no difference, however, in surgical margins (p = 0.578) or reoperation rates (p = 0.430) between the groups. A total of 152 (8.4%) patients were reoperated because of insufficient margins, 96 (8.1%) in the conventional, 56 (9.2%) in the oncoplastic BCS group. The median follow-up time was 75 (2-94) months. There was no difference in local recurrence-free survival between the conventional and oncoplastic BCS groups (log-rank test, p = 0.172). CONCLUSIONS: Oncoplastic BCS was used for larger, multifocal and more aggressive tumours. Nevertheless, no difference in reoperation rate or local recurrences were found. Oncoplastic BCS is as safe as conventional BCS enabling breast conserving for patients who otherwise were candidates for mastectomy.

Breast Lesion Excision System in the diagnosis and treatment of intraductal papillomas - A feasibility study.

OBJECTIVES: This study aims to evaluate the feasibility of Breast Lesion Excision System (BLES) in the treatment of intraductal papillomas. MATERIAL AND METHODS: All patients with a needle biopsy -based suspicion of an intraductal papilloma who consequently underwent a BLES procedure at Helsinki University Hospital between 2011 and 2016 were included in this retrospective study. The purpose of the BLES procedure was either to excise the entire lesion or in few cases to achieve better sampling. RESULTS: In total, 74 patients underwent 80 BLES procedures. Pathological diagnosis after the BLES biopsy confirmed an intraductal papilloma without atypia in 43 lesions, whereas 10 lesions were upgraded to high-risk lesions (HRL) with either atypical ductal hyperplasia or lobular carcinoma in situ. Five cases were upgraded to malignancy, two were invasive ductal carcinomas and three were ductal carcinoma in situ. Additionally, 18 lesions were diagnosed as other benign lesions. Four procedures failed. Complete excision with BLES was achieved in 19 out of 43 intraductal papillomas, 6 out of 10 HRL and two out of five malignant lesions. No major complications occurred. The BLES procedure was adequate in the management of the 71 breast lesions. CONCLUSION: The BLES procedure is an acceptable method for the management of small benign and high-risk breast lesions such as intraductal papillomas in selected patients. Thus, a great amount of diagnostic surgical biopsies can be avoided.