Effectiveness of peer support on health-related quality of life in recently diagnosed breast cancer patients: a randomized controlled trial.

PURPOSE: Breast cancer is the most common cancer of Finnish women. Peer support could be a way to help breast cancer patients to deal with the disease but studies on its effectiveness have produced conflicting results. The aim of this randomized controlled trial was to study the effectiveness of peer support on health-related quality of life (HRQoL) of breast cancer patients. METHODS: Patients with recently diagnosed breast cancer at the Helsinki University Hospital were randomly allocated to intervention (n = 130) or control (n = 130) groups. The intervention group patients received peer support via telephone one to five times according to their preference. The control group received usual care only. HRQoL was assessed with generic (15D) and disease-specific (EORTC QLQ-30 and its breast cancer specific module BR23) instruments at baseline and at 3-, 6-, and 12-month follow-up points. RESULTS: The mean (SD) age of the patients was 60.0 (10.5) years and their baseline mean 15D score 0.922 (0.066). At baseline, the intervention and control groups did not differ from each other. During follow-up, the 15D score deteriorated statistically significantly (p < 0.001) and clinically importantly in both groups but slightly less in the intervention group although the difference was not significant. Regarding individual 15D dimensions, the EORTC-QLQ30, or its breast-specific module, peer support did not show any consistent advantage compared to usual care. CONCLUSION: Peer support had no clear effect on the HRQoL of breast cancer patients.

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study.

BACKGROUND: The prognostic significance of isolated tumour cells (ITCs) in the sentinel nodes (SNs) is controversial in early breast cancer, and some centres have abandoned immunohistochemistry to detect ITCs. METHODS: Patients with unilateral pT1N0 breast cancer, operated between February 2001 and August 2005 at a university hospital were included in this prospective, population-based cohort study. Survival of 936 patients with or without isolated tumour cells (ITC) in their SNs were compared with the log-rank test and Cox regression analysis. RESULTS: Eight hundred sixty one (92.0%) patients were ITC-negative (pN0i-) and 75 (8.0%) ITC-positive (pN0i+). Patients with ITC-positive cancer received more frequently adjuvant systemic therapies than those with ITC-negative cancer. The median follow-up time was 9.5 years. Ten-year distant disease-free survival was 95.3% in the pN0i- group and 88.8% in the pN0i+ group (P = 0.013). ITCs were an independent prognostic factor in a Cox regression model (HR = 2.34, 95% CI 1.09-5.04; P = 0.029), together with tumour Ki-67 proliferation index and diameter. ITCs were associated with unfavourable overall survival (P = 0.005) and breast cancer-specific survival (P = 0.001). CONCLUSIONS: We conclude that presence of ITCs in the SNs is an adverse prognostic factor in early small node-negative breast cancer, and may be considered in the decision-making for adjuvant therapy.

Estrogen biosynthesis in breast adipose tissue during menstrual cycle in women with and without breast cancer.

Circulating estrogens fluctuate during the menstrual cycle but it is not known whether this fluctuation is related to local hormone levels in adipose tissue. We analyzed estrogen concentrations and gene expression of estrogen-regulating enzymes in breast subcutaneous adipose tissue in premenopausal women with (n = 11) and without (n = 17) estrogen receptor-positive breast cancer. Estrone (E1) was the predominant estrogen in premenopausal breast adipose tissue, and E1 and mRNA expression of CYP19A1 in adipose tissue correlated positively with BMI. Adipose tissue estradiol (E2) concentrations fluctuated during the menstrual cycle, similarly to the serum concentrations. In women with breast cancer median adipose tissue E1 (1519 vs. 3244, p < .05) and E2 (404 vs. 889 pmol/kg, p < .05) levels were lower in the follicular than in the luteal phase whereas in control women no significant differences were observed. In the follicular phase, mRNA expressions of HSD17B1 (median 0.06; interquartile range 0.05-0.07 vs. 0.17; 0.03-0.2, p = .010) and CYP19A1 (0.08; 0.07-0.14 vs. 0.22; 0.09-0.54, p = .025) were lower in women with breast cancer than in controls. In conclusion, the changes in adipose tissue E1 and E2 concentrations and the estrogen-regulating CYP19A1 and HSD17B1 during the menstrual cycle may be related to dysfunctional local estrogen metabolism in women with breast cancer.

Inflammations of the mammary gland.

Breast inflammation, i.e. mastitis is an entity with a variable etiology and severity, typically affecting women of fertile age. In most cases, anamnesis reveals the etiology of the disease, bacterial puerperal mastitis associated with breastfeeding being the most common. Periductal mastitis is a breast inflammation typically associated with smoking in women of 40 to 50 years of age, localized to the region of the areola. Granulomatous mastitis and other rare breast inflammations usually require specialized care. Regardless of etiology, treatment of acute inflammation depends on the clinical picture and, with the exception of puerperal mastitis, emergency ultrasound imaging is often necessary in order to detect an abscess and drain it. In all cases of mastitis, the possibility of underlying malignancy as well as inflammatory breast cancer should be kept in mind. If specialized care is required, breast inflammation is treated in a breast, general or plastic surgery unit.

[Breast lump in a young woman]. / Nuoren naisen rintakyhmy.

While a breast lump in a young woman is almost always benign, the lump may also be caused by breast cancer and rare malignant tumors. Factors increasing the risk of breast cancer, and especially the family history in respect of breast cancer and ovarian cancer should be mapped out from the anamnesis. Clinical examination of both breasts and lymph node regions is carried out in a systematic manner. Benignity of the lump must in all cases be confirmed by imaging and when necessary, by taking a core needle biopsy. Among the benign tumors of the breast, only a small symptomless fibroadenoma confirmed by core needle biopsy does not require an assessment by a surgeon.

[Axillary ultrasound for a breast cancer patient and changing international treatment practices]. / Rintasyöpäpotilaan kainalon kaikukuvaus ja muuttuvat kansainväliset hoitokäytännöt.

INTRODUCTION: We explored the effects of novel treatment practices on radiological examinations of the axilla in Finland. PATIENTS AND METHODS: Axillary ultrasound was performed for 178 new breast cancer patients preoperatively. A core biopsy was taken from the suspected lymph nodes, and the finding was compared with the postoperative results. RESULTS: Ultrasound in combination with the core biopsy detects 61.6% of the macrometastases. Ultrasound detected almost all axilla having a high tumor burden. CONLUSIONS: Preoperative axillary ultrasound and core biopsy for suspected lymph nodes before the operation is still recommended for all breast cancer patients. Frozen section examination of the sentinel lymph node can be omitted if preoperatively the primary tumour is unifocal, less than 15mm and the axillary ultrasound finding negative.

The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer.

PURPOSE: The accurate harvesting of a sentinel node in breast cancer includes a sequence of procedures with components from different medical specialities, including nuclear medicine, radiology, surgical oncology and pathology. The aim of this document is to provide general information about sentinel lymph node detection in breast cancer patients. METHODS: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM) have written and approved these guidelines to promote the use of nuclear medicine procedures with high quality. The final result has been discussed by distinguished experts from the EANM Oncology Committee, the SNMMI and the European Society of Surgical Oncology (ESSO). CONCLUSION: The present guidelines for nuclear medicine practitioners offer assistance in optimizing the diagnostic information from the SLN procedure. These guidelines describe protocols currently used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

Pain in 1,000 women treated for breast cancer: a prospective study of pain sensitivity and postoperative pain.

BACKGROUND: This article describes the methods and results of the early part (experimental pain tests and postoperative analgesia) of a study that assesses genetic and other factors related to acute pain and persistent pain after treatment of breast cancer in a prospective cohort of 1,000 women. METHODS: One thousand consenting patients were recruited to the study. Before surgery (breast resection or mastectomy with axillary surgery), the patients filled in questionnaires about health, life style, depression (Beck Depression Inventory), and anxiety (State-Trait Anxiety Inventory). They were also exposed to experimental tests measuring heat (43° and 48°C, 5 s) and cold (2-4°C) pain intensity and tolerance. Anesthesia was standardized with propofol and remifentanil, and postoperative analgesia was optimized with i.v. oxycodone. RESULTS: The patients showed significant interindividual variation in heat and cold pain sensitivity and cold pain tolerance. There was a strong correlation between the experimental pain measures across the tests. Presence of chronic pain, the number of previous operations, and particularly state anxiety were related to increased pain sensitivity. Previous smoking correlated with decreased heat pain sensitivity. These factors explained 4-5% of the total variance in pain sensitivity in these tests. Oxycodone consumption during 20 h was significantly higher in patients who had axillary clearance. Oxycodone consumption had only a weak correlation with the experimental pain measures. CONCLUSIONS: Contact heat and cold pressure tests identify variability in pain sensitivity which is modified by factors such as anxiety, chronic pain, previous surgery, and smoking. High levels of anxiety are connected to increased pain sensitivity in experimental and acute postoperative pain.

Local recurrence of breast cancer after mastectomy and modern multidisciplinary treatment.

BACKGROUND: To study the incidence of local recurrence (LR) of early breast cancer in the ipsilateral thoracic wall after mastectomy and outcome of patients with LR. MATERIAL AND METHODS: A retrospective cohort study based on 2220 consecutive breast cancer patients treated at the Helsinki University Central Hospital, Finland, in 2000 to 2003. A subset of 755 (34.0%) patients had mastectomy which was usually followed by postoperative radiotherapy (51.2%) and/or systemic adjuvant therapy (79.2%). RESULTS: During a median follow-up of 89 months, 22 (2.9%) patients treated with mastectomy had LR. The median time to LR was 27 months. None of the 12 patient- or tumour-related standard risk factors studied were independently associated with LR-free survival in a multivariate model. Six (27.3%) of the 22 patients with LR had distant metastases diagnosed either prior to or simultaneously with LR. The subset of 16 patients who were diagnosed with LR without concomitant distant recurrence had five-year breast cancer-specific survival of 77.5% as calculated from the date of LR detection, and overall survival of 59.2%. CONCLUSIONS: LR after mastectomy has become a rare event. Most women with isolated LR survive for five years after LR.

Effect of delayed autologous breast reconstruction on breast cancer recurrence and survival.

BACKGROUND: The goal of the present study was to evaluate the impact of delayed autologous breast reconstruction on disease relapse in breast cancer patients treated with mastectomy. MATERIAL AND METHODS: The study was based on 503 consecutive patients younger than 70 years of age who underwent mastectomy between January 2000 and December 2003. Overall, 391 (78 %) received mastectomy alone and 112 (22 %) underwent a delayed breast reconstruction. The median time from mastectomy to delayed breast reconstruction was 34 months. The median duration of follow-up was 102 months. RESULTS: There were no locoregional recurrences (LRR) in patients who underwent delayed reconstruction (0.0 %); 21 LRR developed in patients treated with mastectomy only (5.4 %), P = 0.011. Distant metastases occurred less frequently in the reconstruction group (12.5 %) than in the patients who underwent mastectomy alone (21.5 %); P = 0.0343. The 8-year breast cancer specific survival in the reconstruction group was 98.2 and 85.7 % for the mastectomy only group, P = 0.000. CONCLUSIONS: Delayed autologous breast reconstruction does not appear to adversely influence disease progression when compared to patients treated with mastectomy only.

Role of RNA binding protein HuR in ductal carcinoma in situ of the breast.

HuR is a ubiquitously expressed RNA-binding protein that modulates gene expression at the post-transcriptional level. It is predominantly nuclear, but can shuttle between the nucleus and the cytoplasm. While in the cytoplasm HuR can stabilize its target transcripts, many of which encode proteins involved in carcinogenesis. While cytoplasmic HuR expression is a marker of reduced survival in breast cancer, its role in precursor lesions of malignant diseases is unclear. To address this we explored HuR expression in atypical ductal hyperplasia (ADH) and in ductal in situ carcinomas (DCIS). We show that cytoplasmic HuR expression is elevated in both ADH and DCIS when compared to normal controls, and that this expression associated with high grade, progesterone receptor negativity and microinvasion and/or tumour-positive sentinel nodes of the DCIS. To study the mechanisms of HuR in breast carcinogenesis, HuR expression was silenced in an immortalized breast epithelial cell line (184B5Me), which led to reduction in anchorage-independent growth, increased programmed cell death and inhibition of invasion. In addition, we identified two novel target transcripts (CTGF and RAB31) that are regulated by HuR and that bind HuR protein in this cell line. Our results show that HuR is aberrantly expressed at early stages of breast carcinogenesis and that its inhibition can lead to suppression of this process. ArrayExpress Accession No. E-MEXP-3035.

Axillary and supraclavicular recurrences are rare after axillary lymph node dissection in breast cancer.

BACKGROUND: This study was designed to evaluate the incidence of and risk factors for axillary recurrence (AR) and supraclavicular recurrence (SR) in breast cancer patients with axillary lymph node dissection. METHODS: The study was based on 1,180 patients with unilateral invasive breast cancer operated between January 2000 and December 2003. The median duration of follow-up was 78 months. RESULTS: The 7-year AR incidence was 0.7% and SR incidence was 1.3%. Twelve of the 14 SR patients and 4 of the 8 AR patients had concomitant distant recurrences. No risk factors for AR were identified. Histological tumor grade III as well as estrogen and progesterone negativity were risk factors for SR. SR, but not AR, was an independent risk factor for poor breast cancer-specific survival [hazard ratio, 10.116; P < 0.0001]. Among N1 patients, the extent of radiotherapy (RT) had no influence on regional recurrences. Among N2-N3 patients, the 7-year regional recurrence rates were 34.3% in patients without RT, 0% in patients with local RT, and 1.2% in patients with locoregional RT (P < 0.0001). CONCLUSIONS: AR and SR are rare events that often are detected concomitantly with distant metastases. SRs are associated with aggressive disease and poor survival. Our results also suggest that regional RT reduces regional recurrences in N2-N3 patients but not in N1 patients, but the retrospective, nonrandomized study setting renders this conclusion as uncertain.

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.

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.

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.

Comparison of in vitro breast cancer visibility in analyser-based computed tomography with histopathology, mammography, computed tomography and magnetic resonance imaging.

High-resolution analyser-based X-ray imaging computed tomography (HR ABI-CT) findings on in vitro human breast cancer are compared with histopathology, mammography, computed tomography (CT) and magnetic resonance imaging. The HR ABI-CT images provided significantly better low-contrast visibility compared with the standard radiological images. Fine cancer structures indistinguishable and superimposed in mammograms were seen, and could be matched with the histopathological results. The mean glandular dose was less than 1 mGy in mammography and 12-13 mGy in CT and ABI-CT. The excellent visibility of in vitro breast cancer suggests that HR ABI-CT may have a valuable role in the future as an adjunct or even alternative to current breast diagnostics, when radiation dose is further decreased, and compact synchrotron radiation sources become available.

Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p.

MicroRNA-221-3p (miR-221-3p) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation and lipid metabolism are uncharacterized. miR-221-3p or its inhibitor was transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markers SCD1, GLUT4, FAS, DGAT1/2, AP2, ATGL and AdipoQ, whereas the miR-221-3p inhibitor increased TG storage. Knockdown of the predicted miR-221-3p target, 14-3-3γ, had similar antiadipogenic effects as miR-221-3p overexpression, indicating it as a potential mediator of mir-221-3p function. Importantly, miR-221-3p overexpression inhibited de novo lipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression.

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.

Influence of isolated tumor cells in sentinel nodes on outcome in small, node-negative (pT1N0M0) breast cancer.

PURPOSE: To evaluate the prognostic significance of isolated tumor cells found on sentinel node biopsy. METHODS: The study is based on a prospectively followed up cohort of 1,865 consecutive patients diagnosed with pT1 (tumor size

Outcome of selected breast cancer patients with micrometastasis or isolated tumor cells in sentinel node biopsy and no completion axillary lymph node dissection.

BACKGROUND AND OBJECTIVES: Axillary lymph node dissection (ALND) is the standard of care in patients with tumor-positive sentinel nodes (SN). However, approximately half of these patients do not have additional metastases in their axilla and therefore do not benefit from completion ALND. Our aim was to examine the outcome of highly selected breast cancer patients with tumor-positive SN without completion ALND. METHODS: Altogether 48 patients with tumor-positive SN without ALND were included in this study. Twenty-two patients had micrometastasis and 26 had isolated tumor cells (ITC) in their sentinel node biopsy. The median follow-up time was 37 months (range 9-78). RESULTS: No axillary recurrences occurred during the follow-up. One patient had a local recurrence. Distant metastases as the first event were observed in two patients. One of them died in breast cancer. Nine patients died from intercurrent causes. CONCLUSIONS: Omitting ALND seems safe in selected breast cancer patients with SN micrometastasis or ITC.