Compliance with recommended cancer patient pathway timeframes and choice of treatment differed by cancer type and place of residence among cancer patients in Norway in 2015-2016.

BACKGROUND: Cancer patient pathways (CPPs) were implemented in Norway to reduce unnecessary waiting times, regional variations, and to increase the predictability of cancer care for the patients. This study aimed to determine if 70% of cancer patients started treatment within the recommended time frames, and to identify potential delays. METHODS: Patients registered with a colorectal, lung, breast, or prostate cancer diagnosis at the Cancer Registry of Norway in 2015-2016 were linked with the Norwegian Patient Registry and Statistics Norway. Adjusting for sociodemographic variables, multivariable quantile (median) regressions were used to examine the association between place of residence and median time to start of examination, treatment decision, and start of treatment. RESULTS: The study included 20 668 patients. The proportions of patients who went through the CPP within the recommended time frames were highest among colon (84%) and breast (76%) cancer patients who underwent surgery and lung cancer patients who started systemic anticancer treatment (76%), and lowest for prostate cancer patients who underwent surgery (43%). The time from treatment decision to start of treatment was the main source of delay for all cancers. Travelling outside the resident health trust prolonged waiting time and was associated with a reduced odds of receiving surgery and radiotherapy for lung and rectal cancer patients, respectively. CONCLUSIONS: Achievement of national recommendations of the CCP times differed by cancer type and treatment. Identified bottlenecks in the pathway should be targeted to decrease waiting times. Further, CPP guidelines should be re-examined to determine their ongoing relevance.

"It was an important part of my treatment": a qualitative study of Norwegian breast Cancer patients' experiences with mainstreamed genetic testing.

BACKGROUND: In South-Eastern Norway, genetic testing for BRCA1 and BRCA2 is offered to breast cancer patients by their treating surgeon or oncologist. Genetic counselling from a geneticist or a genetic counsellor is offered only to those who test positive for a pathogenic variant or have a family history of cancer. This practice is termed "mainstreamed genetic testing". The aim of this study was to learn about patients' experience of this healthcare service. METHODS: Qualitative in-depth interviews were conducted with 22 breast cancer patients who had been diagnosed during the first half of 2016 or 2017 at one regional and one university hospital and who had been offered testing by their treating physician. A six-phase thematic approach was used to analyse the data. RESULTS: The participants had varied experiences of how and when testing was offered. Three main themes emerged from the analysis: 1. informational and communicational needs and challenges during a chaotic time, 2. the value of genetic testing and 3. the importance of standardised routines for mainstreamed genetic testing. CONCLUSIONS: Despite the shock of their diagnosis and the varying experiences they had in respect of how and when testing was offered, all of the participants emphasised that genetic testing had been an important part of their diagnosis and treatment. Our results indicate that there is a need for continuous collaboration between geneticists, surgeons, oncologists and laboratory specialists in order to establish simple and robust routines so as to ensure that all eligible breast cancer patients are offered testing at a point when the test result can have an impact on treatment.

Breast cancer metastasis: immune profiling of lymph nodes reveals exhaustion of effector T cells and immunosuppression.

Sentinel lymph nodes are the first nodes draining the lymph from a breast and could reveal early changes in the host immune system upon dissemination of breast cancer cells. To investigate this, we performed single-cell immune profiling of lymph nodes with and without metastatic cells. Whereas no significant changes were observed for B-cell and natural killer (NK)-cell subsets, metastatic lymph nodes had a significantly increased frequency of CD8 T cells and a skewing toward an effector/memory phenotype of CD4 and CD8 T cells, suggesting an ongoing immune response. Additionally, metastatic lymph nodes had an increased frequency of TIGIT (T-cell immunoreceptor with Ig and ITIM domains)-positive T cells with suppressed TCR signaling compared with non-metastatic nodes, indicating exhaustion of effector T cells, and an increased frequency of regulatory T cells (Tregs) with an activated phenotype. T-cell alterations correlated with the percentage of metastatic tumor cells, reflecting the presence of metastatic tumor cells driving T effector cells toward exhaustion and promoting immunosuppression by recruitment or increased differentiation toward Tregs. These results show that immune suppression occurs already in early stages of tumor progression.

Postdischarge pain, nausea and patient satisfaction after diagnostic and breast-conserving ambulatory surgery for breast cancer: A cross-sectional study.

BACKGROUND: The aims of this study were to assess first day postdischarge pain, nausea and patient satisfaction in ambulatory breast cancer surgical patients, after diagnostic and breast conserving procedures. METHODS: A total of 781 women, aged 18-85 years were included in this prospective, cross-sectional study. All patients received standardized multimodal pain prophylaxis with paracetamol, COX-II inhibitor, dexamethasone and wound infiltration with local anaesthetics. Nausea prophylaxis was provided with ondansetron. Most patients received general anaesthesia with propofol and remifentanil. Data were collected using a validated questionnaire during telephone follow-up on the first postoperative day. RESULTS: The response rate was 94.5%. NRS ≥ 4 was reported by 5.3% at rest, by 17% during activity and by 30.7% as the worst pain score. Young age was strongly associated with more pain both at rest, during activity and regarding worst pain since discharge. Postdischarge nausea was present in 17.8%, and vomiting in 1.2%. High pain score during activity and higher level of worst pain, were associated with nausea. There was no association between nausea and age, type of anaesthesia, surgical procedure or pain at rest. Patient satisfaction was high (97.8%-99.7%) regarding information, time for discharge and overall satisfaction. CONCLUSION: Pain scores and incidence of nausea were generally low on the day after surgery. Young age was a strong predictor for postdischarge pain. A high worst pain score and high pain score during the activity were associated with postdischarge nausea. Patient satisfaction was high.

Treatment of Ductal Carcinoma in situ: A Register-Based Study of Norwegian Women Diagnosed between 1995 and 2018.

Introduction: The incidence of ductal carcinoma in situ (DCIS) has increased after implementation of mammographic screening. The lesion represents management challenges due to its undetermined growth pattern. We aimed to explore treatment of women aged 48-71 years diagnosed with DCIS between 1995 and 2018, by detection mode and histopathological characteristics. Material and Methods: Data on surgical treatment and radiation therapy (RT) of 4,995 women diagnosed with DCIS were retrieved from the Cancer Registry of Norway. We described the percentage and frequency of breast-conserving treatment (BCT) for participants in BreastScreen Norway (screen-detected) and nonparticipants. We estimated the relative risk (RR) of BCT, using log-binomial regression models. Results: Use of BCT increased from about 40% in 1995 to 85% in 2018. Use of BCT was more common among older than younger women and more commonly used for screen-detected versus tumors detected outside the screening program. Nine out of ten women with tumors ≤10 mm were treated with BCT and two out of ten with tumors >50 mm. RT was given to 89.3% of the women with tumors ≤10 mm, 34.1% of those with tumors classified as van Nuys' grade 1 and <10 mm and 96.0% of the tumors >50 mm. Use of BCT was less common for tumors >50 mm compared to <10 mm (RR adjusted for age, detection mode, van Nuys' grade, and localization: 0.26, 95% CI: 0.19-0.36). Conclusion: BCT was increasingly used among women diagnosed with DCIS in Norway during the period from 1995 to 2018, particularly for screen-detected, small lesions with low van Nuys' grade.

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).

Dietary changes in early-stage breast cancer patients from pre-surgery and over the 12 months post-surgery.

The time after a breast cancer diagnosis is a potential period for making positive dietary changes, but previous results are conflicting. The main aim of the present study was to study breast cancer patients' dietary changes during the 12 months post-surgery and from 12 months pre-surgery to 12 months post-surgery with repeated administration of a 7-d pre-coded food diary and an FFQ, respectively. Women (n 506), mean age 55·3 years diagnosed with invasive breast cancer (stages I and II), were included. The dietary intake was quite stable over time, but the intake was lower for energy (0·3 and 0·4 MJ/d), alcohol (1·9 and 1·5 g/d) and vegetables (17 and 22 g/d) at 6 months than 3 weeks post-surgery (food diary) and at 12 months post-surgery than pre-surgery (FFQ), respectively. Furthermore, energy percentage (E%) from carbohydrates increased between 0·8 and 1·2 E% and E% from fat decreased between 0·6 and 0·8 E% over time, measured by both dietary assessment methods. We observed a higher intake of dairy products (11 g/d) at 6 months post-surgery (food diary), and a lower intake of dairy products (34 g/d) and red and processed meat (7·2 g/d) at 12 months post-surgery (FFQ). Moreover, 24 % of the patients claimed they made dietary changes, but mostly they did not change their diet differently compared with those patients who claimed no changes. In conclusion, breast cancer patients reported only minor dietary changes from 12 months pre-surgery and during the 12 months post-surgery.

Surgical treatment of breast cancer in Norway 2003-2018. / Kirurgisk behandling av brystkreft i Norge 2003­18.

BACKGROUND: Breast-conserving surgery is recommended in Norway and internationally in cases of early-stage breast cancer. We analysed the surgical methods used for breast-cancer patients by hospital providing treatment, age at the time of diagnosis, detection method and histopathological characteristics of the tumours in the period 2003 to 2018. MATERIAL AND METHOD: Data on women of all ages diagnosed with invasive breast cancer (n = 47 004) were retrieved from the Cancer Registry of Norway's databases. We excluded women with distant metastases at the time of diagnosis (n = 1 773) and those for whom no surgical method was recorded (n = 2 638). The detection method was defined as breast cancer detected by screening, in inter-screening intervals, or outside BreastScreen Norway. The surgical methods chosen were compared by means of descriptive analyses. RESULTS: Slightly over half (23 661 of 42 593, i.e. 55.6 %) of the women in whom breast cancer was detected in the study period underwent breast-conserving surgery. The percentage increased from 1 189/2 423 (49.1 %) in 2003 to 2 070/2 958 (70.0 %) in 2018. There were large differences across hospitals. In the period 2015-2018 we found the highest proportion of breast-conserving surgery, 175/187 (93.6 %) for breast cancer detected by screening to be performed at Ålesund Hospital, and the lowest proportion, 121/351 (34.5 %) among women with breast cancer detected outside BreastScreen Norway, to be performed at Radiumhospitalet. Breast-conserving surgery was used most frequently on women with small tumours without spreading to axillary lymph nodes. INTERPRETATION: We found considerable differences in the surgical methods used across hospitals and for different detection methods.

Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER-positive breast cancer.

Antiangiogenic drugs are potentially a useful supplement to neoadjuvant chemotherapy for a subgroup of patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer, but reliable biomarkers for improved response are lacking. Here, we report on a randomized phase II clinical trial to study the added effect of bevacizumab in neoadjuvant chemotherapy with FEC100 (5-fluorouracil, epirubicin and cyclophosphamide) and taxanes (n = 132 patients). Gene expression from the tumors was obtained before neoadjuvant treatment, and treatment response was evaluated by residual cancer burden (RCB) at time of surgery. Bevacizumab increased the proportion of complete responders (RCB class 0) from 5% to 20% among patients with estrogen receptor (ER) positive tumors (P = .02). Treatment with bevacizumab was associated with improved 8-year disease-free survival (P = .03) among the good responders (RCB class 0 or I). Patients treated with paclitaxel (n = 45) responded better than those treated with docetaxel (n = 21; P = .03). Improved treatment response was associated with higher proliferation rate and an immune phenotype characterized by high presence of classically activated M1 macrophages, activated NK cells and memory activated CD4 T cells. Treatment with bevacizumab increased the number of adverse events, including hemorrhage, hypertension, infection and febrile neutropenia, but despite this, the ECOG status was not affected.

Cosmetic breast implants and breast cancer. / Kosmetiske brystimplantater og brystkreft.

BACKGROUND: The number of women with cosmetic breast implants has increased in recent decades in Norway. We compared the risk of detecting breast cancer and histopathological characteristics of the tumours in women with and without implants. MATERIAL AND METHOD: We retrieved information from the Cancer Registry's databases on implants and breast cancer among women who had participated in BreastScreen Norway in the period 1996-2016. Use of the data is pursuant to the Cancer Registry Regulations. We identified 785 706 women, of whom 10 086 (1.3 %) reported that they had an implant. We calculated the incidence rate ratio (IRR) with a 95 % confidence interval (95 % CI) for detected breast cancer and compared histopathological tumour characteristics among women with and without implants with the aid of descriptive analyses. RESULTS: The incidence rate ratio for breast cancer was 30 % lower for women with implants than for women without (IRR 0.70 (95 % CI 0.60-0.81)). Women with implants who had cancer detected had tumours with a larger diameter than women without, and several of these women had metastasis to axillary lymph nodes. INTERPRETATION: Women with implants who participated in BreastScreen Norway had a lower risk of detection of breast cancer, but more advanced disease upon diagnosis than those without implants. This may be due to the difficulty caused by implants in performing and interpreting the mammograms. The women should be informed about this before undergoing augmentation mammoplasty.

Mainstreamed genetic testing of breast cancer patients in two hospitals in South Eastern Norway.

Studies have shown that a significant number of eligible breast cancer patients are not offered genetic testing or referral to genetic counseling. To increase access to genetic testing in South Eastern Norway, testing has since 2014 been offered directly to breast cancer patients by surgeons and oncologists. This practice is termed "mainstreamed genetic testing". The aim of this study was to investigate to what extent patients in South Eastern Norway are offered testing. Three hundred and sixty one patients diagnosed in 2016 and 2017 at one regional and one university hospital in South Eastern Norway were included. Data on whether the patients fulfilled the criteria, whether they had been offered testing and if they were tested were collected. In total, 26.6% (96/361) fulfilled the criteria for testing. Seventy five percent (69/92) of these were offered testing, and 71.7% (66/92) were tested. At the university hospital, 90.2% (37/41) of eligible patients were offered testing, and at the regional hospital 62.7% (32/51). Fifty two percent (12/23) of eligible patient not offered testing were younger than 50 years at time of diagnosis. As many as 95.4% (125/131) of all patients who were offered testing, wanted to be tested. The majority of patients who fulfilled the criteria were offered testing, supporting the practice of mainstreamed genetic testing. There were nevertheless differences in rates of testing between the hospitals that affected all groups of patients, indicating that genetic testing may not be equally accessible to all patients. We suggest that efforts should be made to increase awareness and improve routines for genetic testing of breast cancer patients in Norway.

The Role of Calcitonin in Predicting the Extent of Surgery in Medullary Thyroid Carcinoma: A Nationwide Population-Based Study in Norway.

BACKGROUND: Preoperative predictors for the need of prophylactic lymph node dissection in the lateral neck have been studied in patients with medullary thyroid carcinoma (MTC). OBJECTIVES: To evaluate the ability of serum calcitonin to predict the extent of surgery needed in the lateral neck. METHODS: This retrospective population-based cohort study includes data from 94 of 139 patients with MTC surgically treated in Norway from 2003 to 2016. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway, and grouped according to calcitonin levels. In 58 patients without distant metastases or disease progression to the next tumor level (NPNL), data were compared in prognostic groups (N0-NPNL), (N1a-NPNL), and (N1b-NPNL). RESULTS: At calcitonin levels ≤500, 501-1,000, and >1,000 pmol/L, metastatic lymph nodes in the lateral neck were found in 16, 50, and 71% of the patients, respectively. In the prognostic groups, 19% of N0-NPNL patients had calcitonin >500 pmol/L and 17% of N1b-NPNL patients had calcitonin ≤500 pmol/L. In multivariate analysis, factors predicting biochemical cure and calcitonin level ≤500 pmol/L were no metastatic lymph nodes in the lateral neck (p = 0.030) and tumor diameter ≤20 mm (p < 0.001), respectively. Factors related to metastatic lymph nodes in the lateral neck were extrathyroidal extension (p = 0.007) and no biochemical cure (p = 0.028). CONCLUSIONS: Basal calcitonin cannot predict the need for prophylactic lateral lymph node dissection in patients with MTC. Further prospective, randomized studies are warranted.

Breast cancer quantitative proteome and proteogenomic landscape.

In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.

Using clinical cancer registry data for estimation of quality indicators: Results from the Norwegian breast cancer registry.

INTRODUCTION: Increased focus on quality indicators and the use of clinical registries for breast cancer for real world studies have shown higher compliance to recommended therapy and better survival. In 2010, the European Society of Breast Cancer Specialist (EUSOMA) proposed quality indicators (QI) covering diagnosis, treatment and follow-up. To become a EUSOMA certified Breast Cancer Unit, 14 specified quality indicators, in addition to other requirements, need to be met. To evaluate the compliance and results of recommended treatment in breast cancer care in Norway and to improve the quality of epidemiological data, the Cancer Registry of Norway (CRN) in cooperation with the Norwegian Breast Cancer Group (NBCG) developed the Norwegian Breast Cancer Registry (NBCR). The objective of this study is to assess the feasibility of using the NBCR for estimating the EUSOMA QI individually for all hospitals diagnosing and treating breast cancer in Norway. METHODS: To provide researchers with high quality cancer data as well as for the purpose of national cancer statistics, the CRN employs a cancer registry system to 1) longitudinal capture data from all patients from all medical entities that diagnose and/or treat cancer patients (e.g., pathology, radiology and clinical departments) in Norway; 2) curate data, i.e. validate the correctness of collected data, and assemble the validated cancer data as cancer cases; 3) provide data for analytics and presentation. Estimates for 10 EUSOMA QI were calculated at national and hospital level. To compare hospitals, a summary score of QIs was defined for each hospital. RESULTS: All hospitals currently treating breast cancer patients have the technical ability to submit data to the NBCR for estimation of QIs defined by EUSOMA. Data from pathology and surgery are of high quality. However, data from oncological and radiological departments are incomplete, but improving. This currently hinders three QIs from being calculated. QI on benign to malign diagnosis needs to be calculated at the individual Breast Centre. Over time the adherence to guidelines have improved and the hospital variation for the respective QI have decreased. Two hospitals met all minimum standard on ten QIs in year 2016 and one hospital did not meet one minimum standard, but met all other targets. CONCLUSION: The NBCR has since 2012 published annual reports on breast cancer care and for the year 2016 measured 10 of 14 QI defined by EUSOMA. Increased compliance of recommended treatment in Norway has been observed during the years the registry has been active.

Trends in Diagnostics, Surgical Treatment, and Prognostic Factors for Outcomes in Medullary Thyroid Carcinoma in Norway: A Nationwide Population-Based Study.

BACKGROUND: Medullary thyroid carcinoma (MTC) is rare. Nationwide population-based studies are important to evaluate its clinical course. OBJECTIVES: To describe all patients with MTC in Norway during 1994-2016 and compare time-related trends in diagnostics and surgical treatment, including prognostic factors for biochemical cure and disease-specific survival (DSS). METHODS: This retrospective population-based cohort study includes data for 228 out of 237 patients (96%) with MTC; 201 patients were surgically treated. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway. Data were collected from patients' files. Trends were compared over 2 study periods. RESULTS: MTC accounted for 4.2% of thyroid carcinomas. During the study periods, the incidence increased from 0.18 to 0.25: 100,000 per year, preoperative diagnostics improved with increased use of calcitonin, ultrasound, and fine-needle cytology (p = 0.010, p < 0,001, and p = 0.001), patients were diagnosed at an earlier tumor stage (p = 0.004), and more patients were cured (p = 0.002). Via multivariate analysis of patients with metastatic lymph nodes, independent prognostic factors for cure were: a low ratio of metastatic and total number of dissected lymph nodes (p = 0.021) and no extrathyroidal extension (p = 0.030). Independent prognostic factors for DSS were: no distant metastasis, a younger age, and a low ratio of metastatic and dissected lymph nodes (p = 0.005, p = 0.020, p = 0.022). CONCLUSIONS: Preoperative diagnostics have improved over time with increased therapeutic control. A low ratio of metastatic and dissected lymph nodes predicts better outcomes in patients with metastatic lymph nodes.

Metabolite and lipoprotein responses and prediction of weight gain during breast cancer treatment.

BACKGROUND: Breast cancer treatment has metabolic side effects, potentially affecting risk of cardiovascular disease (CVD) and recurrence. We aimed to compare alterations in serum metabolites and lipoproteins during treatment between recipients and non-recipients of chemotherapy, and describe metabolite profiles associated with treatment-related weight gain. METHODS: This pilot study includes 60 stage I/II breast cancer patients who underwent surgery and were treated according to national guidelines. Serum sampled pre-surgery and after 6 and 12 months was analysed by MR spectroscopy and mass spectrometry. In all, 170 metabolites and 105 lipoprotein subfractions were quantified. RESULTS: The metabolite and lipoprotein profiles of chemotherapy recipients and non-recipients changed significantly 6 months after surgery (p < 0.001). Kynurenine, the lipid signal at 1.55-1.60 ppm, ADMA, 2 phosphatidylcholines (PC aa C38:3, PC ae C42:1), alpha-aminoadipic acid, hexoses and sphingolipids were increased in chemotherapy recipients after 6 months. VLDL and small dense LDL increased after 6 months, while HDL decreased, with triglyceride enrichment in HDL and LDL. At baseline, weight gainers had less acylcarnitines, phosphatidylcholines, lyso-phosphatidylcholines and sphingolipids, and showed an inflammatory lipid profile. CONCLUSION: Chemotherapy recipients exhibit metabolic changes associated with inflammation, altered immune response and increased risk of CVD. Altered lipid metabolism may predispose for treatment-related weight gain.

NR2F1 stratifies dormant disseminated tumor cells in breast cancer patients.

BACKGROUND: The presence of disseminated tumor cells (DTCs) in bone marrow (BM) is an independent prognostic factor in early breast cancer but does not uniformly predict outcome. Tumor cells can persist in a quiescent state over time, but clinical studies of markers predicting the awakening potential of DTCs are lacking. Recently, experiments have shown that NR2F1 (COUP-TF1) plays a key role in dormancy signaling. METHODS: We analyzed the NR2F1 expression in DTCs by double immunofluorescence (DIF) staining of extra cytospins prepared from 114 BM samples from 86 selected DTC-positive breast cancer patients. Samples collected at two or more time points were available for 24 patients. Fifteen samples were also analyzed for the proliferation marker Ki67. RESULTS: Of the patients with detectable DTCs by DIF, 27% had ≥ 50% NR2F1high DTCs, chosen a priori as the cut-off for "dormant profile" classification. All patients with systemic relapse within 12 months after BM aspiration carried ≤ 1% NR2F1high DTCs, including patients who transitioned from having NR2F1high-expressing DTCs in previous BM samples. Of the patients with serial samples, half of those with no relapse at follow-up had ≥ 50% NR2F1high DTCs in the last BM aspiration analyzed. Among the 18 relapse-free patients at the time of the last DTC-positive BM aspiration with no subsequent BM analysis performed, distant disease-free intervals were favorable for patients carrying ≥ 50% NR2F1high DTCs compared with those with predominantly NR2F1low DTCs (p = 0.007, log-rank). No survival difference was observed by classification according to Ki67-expressing DTCs (p = 0.520). CONCLUSIONS: Our study translates findings from basic biological analysis of DTC dormancy to the clinical situation and supports further clinical studies of NR2F1 as a marker of dormancy.

Validation of repeated self-reported n-3 PUFA intake using serum phospholipid fatty acids as a biomarker in breast cancer patients during treatment.

BACKGROUND: The role of n-3 polyunsaturated fatty acids (PUFAs) in breast cancer is not clear and under debate. To explore this relationship it is important to have proper validated dietary assessment methods for measuring the intake of n-3 PUFAs. The aim of the current study is to validate two different methods used to assess the intake of selected n-3 PUFAs as well as food sources of long-chained n-3 PUFAs. Also, we aim to study how stable the intake of fatty acids is during breast cancer treatment. METHODS: The study-population was patients with breast cancer (Stages I-II) or ductal carcinoma in situ (DCIS-grade III) undergoing treatment (n = 49) in Norway. Dietary intake was assessed by two self-administered methods, a 256 food item food frequency questionnaire (FFQ) and a 7-day pre-coded food diary (PFD). The FFQ was administered presurgery and twelve months postsurgery, and the PFD was administered shortly after surgery (10 +/- 2 days), six and twelve months postsurgery. Fasting blood samples (presurgery, six and twelve months postsurgery) were analysed for serum phospholipid fatty acids, a biomarker for intake of n-3 PUFAs. RESULTS: Mean (SD) age was 54.2 (7.8) years at diagnosis, and the mean (SD) body mass index (BMI) was 24.8 (3.4) kg/m2. Correlation coefficients between dietary intakes of n-3 PUFAs measured with the FFQ and the PFD ranged from 0.35 to 0.66. The correlation coefficients between the PFD and the biomarker (serum phospholipid n-3 PUFAs) as well as between the FFQ and the biomarker demonstrated stronger correlations twelve months after surgery (ρ 0.40-0.56 and 0.36-0.53, respectively) compared to around surgery (ρ 0.08-0.20 and 0.28-0.38, respectively). The same pattern was observed for intake of fatty fish. The intake of n-3 PUFAs did not change during treatment assessed by the FFQ, PFD or biomarker. CONCLUSION: These results indicate that the FFQ and the PFD can be used to assess dietary intake of fish and n-3 PUFAs in breast cancer patients during breast cancer treatment. Still, the PFD shortly after surgery should be used with caution. The diet of patients undergoing breast cancer treatment was quite stable, and the intake of n-3 PUFAs did not change.