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.

Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women.

PURPOSE: Family history (FH) and pathogenic variants (PVs) are used for guiding risk surveillance in selected high-risk women but little is known about their impact for breast cancer screening on population level. In addition, polygenic risk scores (PRSs) have been shown to efficiently stratify breast cancer risk through combining information about common genetic factors into one measure. METHODS: In longitudinal real-life data, we evaluate PRS, FH, and PVs for stratified screening. Using FinnGen (N = 117,252), linked to the Mass Screening Registry for breast cancer (1992-2019; nationwide organized biennial screening for age 50-69 years), we assessed the screening performance of a breast cancer PRS and compared its performance with FH of breast cancer and PVs in moderate- (CHEK2)- to high-risk (PALB2) susceptibility genes. RESULTS: Effect sizes for FH, PVs, and high PRS (>90th percentile) were comparable in screening-aged women, with similar implications for shifting age at screening onset. A high PRS identified women more likely to be diagnosed with breast cancer after a positive screening finding (positive predictive value [PPV], 39.5% [95% CI, 37.6 to 41.5]). Combinations of risk factors increased the PPVs up to 45% to 50%. A high PRS conferred an elevated risk of interval breast cancer (hazard ratio [HR], 2.78 [95% CI, 2.00 to 3.86] at age 50 years; HR, 2.48 [95% CI, 1.67 to 3.70] at age 60 years), and women with a low PRS (<10th percentile) had a low risk for both interval- and screen-detected breast cancers. CONCLUSION: Using real-life screening data, this study demonstrates the effectiveness of a breast cancer PRS for risk stratification, alone and combined with FH and PVs. Further research is required to evaluate their impact in a prospective risk-stratified screening program, including cost-effectiveness.

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.

Reoperation rate of ductal carcinoma in situ: impact of tomosynthesis (3D) and spot magnification.

BACKGROUND: Surgical planning depends on precise preoperative assessment of the radiological extent of ductal carcinoma in situ (DCIS). Despite different modalities used, reoperation rates for DCIS due to involved margins are high. PURPOSE: To evaluate the impact of additional imaging views (spot magnification, tomosynthesis) on surgical reoperation rate of DCIS. MATERIAL AND METHODS: The retrospective single institute study includes 157 patients with biopsy-proven pure DCIS seen on mammogram as microcalcifications and treated with breast-conserving surgery. Patients have been divided into three groups according to additional imaging performed: spot magnification, tomosynthesis, and none. All breast images (mammograms, spot magnification, tomosynthesis) were reviewed and the maximum extent of pathological microcalcifications was recorded. Radiological size was compared to final histopathological size. Reoperation rate due to inadequate margins was recorded. RESULTS: Reoperation rates (25%) due to inadequate margins were as follows: spot (18%), tomosynthesis (27%), none (31%); P = 0.488. Spot magnification, tomosynthesis, and digital zoom of full-field digital mammography predicted similarly the final histopathological size. Reoperation group had a significantly greater preoperative radiological median size (26 mm vs. 20 mm; P = 0.014) as well as median size of disease on final histopathological report (29 mm vs. 14 mm; P < 0.001). Discrepancy between radiological and final histopathological size became greater with increasing DCIS extent. CONCLUSION: The main factors for reoperations are DCIS size and discordance between radiological and histopathological sizes. The use of additional imaging views (spot magnification, tomosynthesis) did not reduce reoperation rate.

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.

Delay in the initiation of adjuvant chemotherapy in patients with breast cancer with mastectomy with or without immediate breast reconstruction.

BACKGROUND: Patients with breast cancer undergoing mastectomy should be offered the option of immediate breast reconstruction (IBR). The aim of this retrospective study was to assess whether there is a delay in the initiation of adjuvant chemotherapy in patients undergoing mastectomy with or without IBR. METHOD: The study included patients aged 70 years or younger with clinically node-negative breast cancer who underwent unilateral mastectomy with IBR (IBR group) or mastectomy alone (no-IBR group) followed by adjuvant chemotherapy at the Helsinki University Hospital between January 2012 to July 2018. RESULTS: A total of 645 patients were included; 186 in the IBR group and 459 in the no-IBR group. Sixty-six (35.5 per cent) patients in the IBR group and 102 (22.2 per cent) patients in the no-IBR group received their first chemotherapy cycle later than 6 weeks after surgery (P < 0.001). The respective numbers for later than 8 weeks were 17 (9.1 per cent) and 14 (3.1 per cent) (P = 0.001). Among all 645 patients, postoperative complications were a significant risk factor for a delay in the initiation of chemotherapy. Sixty-seven (39.9 per cent) patients with and 101 (21.2 per cent) patients without complications had a delay in chemotherapy (P < 0.001). The delay in chemotherapy was due to complications in 39 (59.1 per cent) in the IBR group and in 28 (27.5 per cent) in the no-IBR group (P < 0.001). CONCLUSION: Patients undergoing mastectomy alone were more likely to receive adjuvant chemotherapy within 6 weeks after surgery compared with the IBR patients. IBR significantly increased the risk of postoperative complications in comparison with mastectomy alone. The complications, in turn, were a significant risk factor for delay in adjuvant chemotherapy.

Long-Term Survival Outcomes of Patients with Small (≤1 cm) Node-Negative HER2-Positive Breast Cancer Not Treated with Adjuvant Anti-HER2-Targeted Therapy: A 10-Year Follow-Up Study.

Introduction: Human epidermal growth factor receptor 2 (HER2) expression is considered an unfavourable prognostic factor in early breast cancer when the patients are not treated with HER2-targeted therapy. However, the long-term prognostic importance of HER2 expression in small (≤1 cm, stage pT1a-b), node-negative HER2* breast cancer is still incompletely known. Methods: A retrospective analysis was performed based on a prospectively collected database including patients with pT1 breast cancer operated at the Helsinki University Hospital, Finland, between March 2000 and April 2006. In this database, 44 patients with pT1a-bN0M0, HER2* cancer, not treated with adjuvant anti-HER2-targeted therapy (the HER2* group) and 291 pT1a-bN0M0, hormone receptor-positive, HER2-negative cancers (the ER*/HER2- group) were identified and included in the study. Survival outcomes were analysed using the Kaplan-Meier method. Results: The median follow-up time was 9.7 years after primary breast surgery. Ten-year distant disease-free survival (DDFS) was 84.0% in the HER2* group and 98.2% in the ER*/HER2- group (p < 0.001). Ten-year overall survival was only 78.5% in the HER2* group, but 91.7% in the ER*/HER2- group (p = 0.09). Conclusions: Cancer HER2 status is strongly associated with unfavourable DDFS during the first decade of follow-up in patients with small (pT1a-bN0M0) breast cancer when adjuvant anti-HER2-targeted treatment is not administered.

Oncological Safety of Skin-Sparing Mastectomy and Immediate Breast Reconstruction in Extensive Ductal Carcinoma In Situ.

INTRODUCTION: Skin-sparing mastectomy (SSM) with immediate breast reconstruction is the ideal treatment for interested and suitable patients with extensive ductal carcinoma in situ (DCIS). There is no guideline to indicate on how large DCIS the procedure can be performed safely. The primary target of this study was to define the oncological safety of SSM in extensive pure DCIS. The secondary target was to find predictive factors for DCIS upstaging to invasive disease. MATERIALS AND METHODS: A total of 71 consecutive patients with extensive pure DCIS and undergoing SSM with immediate latissimus dorsi (LD) breast reconstruction were retrospectively evaluated. RESULTS: The median size of DCIS lesion in preoperative imaging was 60 mm, the median weight of mastectomy specimen was 350 g, and the median resection margin (RM) was 2.0 mm. A total of 20 patients (28%) had an RM less than 0.5 mm and nine patients (13%) had ink positive margins. Six patients having positive RM underwent reoperation. A total of 29 patients (41%) presented invasive cancer foci in final histopathological assessment and nine patients (13%) had an axillary metastasis. Adjuvant therapy was given to 23 patients presenting invasive cancer. There were no local recurrences or distant metastases (0%, 95% confidence interval 0-0.051) during the mean follow-up of 71 mo. None of the factors evaluated predicted upstaging to invasive disease. CONCLUSIONS: SSM with immediate breast reconstruction in patients with extensive DCIS is oncologically safe even when the margins are close or positive. Additional invasive foci and solitary axillary lymph node metastases are frequent but do not worsen the outcome.

Same-day mastectomy and axillary lymph node dissection is safe for most patients with breast cancer.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the safety of same-day mastectomy, with or without a sentinel node biopsy (SNB) and/or axillary lymph node dissection (ALND). METHODS: In this retrospective study, we reviewed 913 consecutive women who underwent a simple mastectomy for breast cancer between the years 2014 and 2019 and were treated either with same-day surgery (SDS) or an overnight stay (OS) regime. We reviewed all surgical complications, any unplanned return to care (RTC) and the rehospitalization rate for 30 postoperative days. RESULTS: A total of 259 patients (28%) were treated with SDS and 654 patients (72%) with an OS regime. There was no difference in RTC (odds ratio: 0.79 [95% confidence interval: 0.53-1.18], p = 0.26) or any major complications between the groups. None of the investigated subgroups, such as patients with previous neoadjuvant therapy, diabetes, obesity (up to a body mass index of 40 kg/m2 ), the American Society of Anaesthesiologist Class of 3, or elderly patients aged 75-84 years, showed an increased complication rate when treated with the SDS regime. CONCLUSION: A same-day simple mastectomy is safe with SNB and/or ALND. It can be performed safely for most patients with stable co-morbidities.

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.

Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer.

Breast cancer is now globally the most frequent cancer and leading cause of women's death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ERα-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ERα + breast cancer models. The ERα + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ERα signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK.

Breast reconstruction after breast cancer surgery - persistent pain and quality of life 1-8 years after breast reconstruction.

OBJECTIVES: To assess the long-term outcome of breast reconstructions with special focus on chronic postsurgical pain (CPSP) in a larger cohort of breast cancer survivors. METHODS: A cross-sectional study on 121 women with mastectomy and breast reconstruction after mean 2 years 4 months follow up. The mean time from breast reconstruction to the follow-up visit was 4 years 2 months. We studied surveys on pain (Brief Pain Inventory, BPI and Douleur Neuropathique 4, DN4), quality of life (RAND-36 health survey), sleep (insomnia severity questionnaire, ISI), mood (Beck's Depression Index, BDI; Hospital Anxiety and Depression Scale, HADS), and a detailed clinical sensory status. Patients were divided into three groups: abdominal flap (Deep inferior epigastric perforator flap, DIEP; Free transverse rectus abdominis flap, fTRAM, and Pedicled transverse rectus abdominis flap, pTRAM), dorsal flap (Latissimus dorsi flap, LD and Thoracodorsal artery perforator flap, TDAP), and other (Transverse myocutaneous gracilis flap, TMG; implant). Clinically meaningful pain was defined ≥ 4/10 on a numeric rating scale (NRS). We used patients' pain drawings to localize the pain. We assessed preoperative pain NRS from previous data. RESULTS: 106 (87.6%) of the patients did not have clinically meaningful persistent pain. We found no statistically significant difference between different reconstruction types with regards to persistent pain (p=0.40), mood (BDI-II, p=0.41 and HADS A, p=0.54) or sleep (p=0.14), respectively. Preoperative pain prior to breast reconstruction surgery correlated strongly with moderate or severe CPSP. CONCLUSIONS: Moderate to severe CPSP intensity was present in 14% of patients. We found no significant difference in the prevalence of pain across different reconstruction types. Preoperative pain associated significantly with postoperative persistent pain.

The role of polygenic risk and susceptibility genes in breast cancer over the course of life.

Polygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer, and that the PRS can considerably improve risk assessment among their female first-degree relatives. In more detail, women with the c.1592delT variant in PALB2 (242-fold enrichment in Finland, 336 carriers) and an average PRS (10-90th percentile) have a lifetime risk of breast cancer at 55% (95% CI 49-61%), which increases to 84% (71-97%) with a high PRS ( > 90th percentile), and decreases to 49% (30-68%) with a low PRS ( < 10th percentile). Similarly, for c.1100delC in CHEK2 (3.7-fold enrichment; 1648 carriers), the respective lifetime risks are 29% (27-32%), 59% (52-66%), and 9% (5-14%). The PRS also refines the risk assessment of women with first-degree relatives diagnosed with breast cancer, particularly among women with positive family history of early-onset breast cancer. Here we demonstrate the opportunities for a comprehensive way of assessing genetic risk in the general population, in breast cancer patients, and in unaffected family members.

Global trends of hand and wrist trauma: a systematic analysis of fracture and digit amputation using the Global Burden of Disease 2017 Study.

BACKGROUND: As global rates of mortality decrease, rates of non-fatal injury have increased, particularly in low Socio-demographic Index (SDI) nations. We hypothesised this global pattern of non-fatal injury would be demonstrated in regard to bony hand and wrist trauma over the 27-year study period. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 was used to estimate prevalence, age-standardised incidence and years lived with disability for hand trauma in 195 countries from 1990 to 2017. Individual injuries included hand and wrist fractures, thumb amputations and non-thumb digit amputations. RESULTS: The global incidence of hand trauma has only modestly decreased since 1990. In 2017, the age-standardised incidence of hand and wrist fractures was 179 per 100 000 (95% uncertainty interval (UI) 146 to 217), whereas the less common injuries of thumb and non-thumb digit amputation were 24 (95% UI 17 to 34) and 56 (95% UI 43 to 74) per 100 000, respectively. Rates of injury vary greatly by region, and improvements have not been equally distributed. The highest burden of hand trauma is currently reported in high SDI countries. However, low-middle and middle SDI countries have increasing rates of hand trauma by as much at 25%. CONCLUSIONS: Certain regions are noted to have high rates of hand trauma over the study period. Low-middle and middle SDI countries, however, have demonstrated increasing rates of fracture and amputation over the last 27 years. This trend is concerning as access to quality and subspecialised surgical hand care is often limiting in these resource-limited regions.

Falls in older aged adults in 22 European countries: incidence, mortality and burden of disease from 1990 to 2017.

INTRODUCTION: Falls in older aged adults are an important public health problem. Insight into differences in fall-related injury rates between countries can serve as important input for identifying and evaluating prevention strategies. The objectives of this study were to compare Global Burden of Disease (GBD) 2017 estimates on incidence, mortality and disability-adjusted life years (DALYs) due to fall-related injury in older adults across 22 countries in the Western European region and to examine changes over a 28-year period. METHODS: We performed a secondary database descriptive study using the GBD 2017 results on age-standardised fall-related injury in older adults aged 70 years and older in 22 countries from 1990 to 2017. RESULTS: In 2017, in the Western European region, 13 840 per 100 000 (uncertainty interval (UI) 11 837-16 113) older adults sought medical treatment for fall-related injury, ranging from 7594 per 100 000 (UI 6326-9032) in Greece to 19 796 per 100 000 (UI 15 536-24 233) in Norway. Since 1990, fall-related injury DALY rates showed little change for the whole region, but patterns varied widely between countries. Some countries (eg, Belgium and Netherlands) have lost their favourable positions due to an increasing fall-related injury burden of disease since 1990. CONCLUSIONS: From 1990 to 2017, there was considerable variation in fall-related injury incidence, mortality, DALY rates and its composites in the 22 countries in the Western European region. It may be useful to assess which fall prevention measures have been taken in countries that showed continuous low or decreasing incidence, death and DALY rates despite ageing of the population.

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.

Surgical treatment and prognosis of breast cancer in elderly - A population-based study.

BACKGROUND: The aim of this study was to investigate outcome of treatment in patients over 80 years of age with early breast cancer at the time of the diagnosis with special interest in surgical treatment. MATERIALS AND METHODS: Breast cancer patients older than 80 years of age, treated at the Breast Surgery Unit of Helsinki University Hospital in 2005-2010 were identified from electronic patient records. Patients were followed-up until the end of 2014. Patient and tumour characteristics, recurrences, co-morbidities and reasons for omission of surgery were collected from electronic patient records. Survival data was obtained from Finnish Cancer Registry. RESULTS: 446 patients were eligible for the study: 401 (90%) received surgery. The median follow-up time was 52 months. In the entire study population, local and regional recurrences/disease progression were diagnosed in 16 (3.6%) and 6 (1.3%) patients, respectively. The five-year overall survival was 50.6% in the surgical treatment and only 15.2% in non-surgical treatment group, p < 0.001. Also, the five-year breast cancer specific survival was significantly better in the patients with surgery, 82.0%, but 56.0% in the patients without surgery, p < 0.001. There was no mortality related to the surgery, but 122 (30%) patients died within three years from surgery. CONCLUSION: Surgical treatment rate was high. OS and BCSS were better in surgically treated elderly patients. Local and regional disease control was excellent, probably due to high rate of surgical treatment. Surgical treatment also seemed safe in this elderly patient population. However, surgical overtreatment was obvious in some patients.

What makes surgical nerve injury painful? A 4-year to 9-year follow-up of patients with intercostobrachial nerve resection in women treated for breast cancer.

Nerve injury during breast cancer surgery can cause neuropathic pain (NP). It is not known why some, but not all, patients develop chronic postsurgical neuropathic pain (CPSNP) after the same nerve injury. In this study, we examined 251 breast cancer survivors with surgeon-verified intercostobrachial nerve resection to identify factors that associate with CPSNP. The patients were recruited from a previous study of 1000 women treated for breast cancer in 2006 to 2010. This enabled us to analyze preoperative factors that associate with future CPSNP. The patients were re-examined in 2014 to 2016 to diagnose CPSNP using the revised NP diagnostic criteria. Preoperative assessments were pain in the area to be operated on, any chronic pain condition, depressive symptoms, anxiety, sleep, and experimental cold pain sensitivity using the cold pressor test (CPT). Follow-up assessments were CPT, psychological factors, sleep, any chronic pain, and basic laboratory tests. One hundred thirty-seven (55%) patients with intercostobrachial nerve resection fulfilled CPSNP diagnostic criteria after 4 to 9 years. Of them, 30 patients (22%) had moderate to severe pain in self-reports and 86 (63%) presented moderate to severe evoked pain at examination. Preoperative pain in the surgical area, other chronic pains, and breast-conserving surgery were associated with future CPSNP. Other chronic pains, increased psychological burden, and insomnia, both before surgery and at the follow-up, were associated with CPSNP. Preoperative CPT did not associate with future CPSNP. Patients with established CPSNP showed increased pain sensitivity in CPT and higher levels of inflammatory markers, suggesting that central sensitization and inflammation may associate with the maintenance of CPSNP.

Machine-learning-derived classifier predicts absence of persistent pain after breast cancer surgery with high accuracy.

BACKGROUND: Prevention of persistent pain following breast cancer surgery, via early identification of patients at high risk, is a clinical need. Supervised machine-learning was used to identify parameters that predict persistence of significant pain. METHODS: Over 500 demographic, clinical and psychological parameters were acquired up to 6 months after surgery from 1,000 women (aged 28-75 years) who were treated for breast cancer. Pain was assessed using an 11-point numerical rating scale before surgery and at months 1, 6, 12, 24, and 36. The ratings at months 12, 24, and 36 were used to allocate patents to either "persisting pain" or "non-persisting pain" groups. Unsupervised machine learning was applied to map the parameters to these diagnoses. RESULTS: A symbolic rule-based classifier tool was created that comprised 21 single or aggregated parameters, including demographic features, psychological and pain-related parameters, forming a questionnaire with "yes/no" items (decision rules). If at least 10 of the 21 rules applied, persisting pain was predicted at a cross-validated accuracy of 86% and a negative predictive value of approximately 95%. CONCLUSIONS: The present machine-learned analysis showed that, even with a large set of parameters acquired from a large cohort, early identification of these patients is only partly successful. This indicates that more parameters are needed for accurate prediction of persisting pain. However, with the current parameters it is possible, with a certainty of almost 95%, to exclude the possibility of persistent pain developing in a woman being treated for breast cancer.