Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases.

BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).

Long-term Survival after Volatile or Propofol General Anesthesia for Bladder Cancer Surgery: A Retrospective National Registry Cohort Study.

BACKGROUND: Prospective interventional trials and retrospective observational analyses provide conflicting evidence regarding the relationship between propofol versus inhaled volatile general anesthesia and long-term survival after cancer surgery. Specifically, bladder cancer surgery lacks prospective clinical trial evidence. METHODS: Data on bladder cancer surgery performed under general anesthesia between 2014 and 2021 from the National Quality Registry for Urinary Tract and Bladder Cancer and the Swedish Perioperative Registry were record-linked. Overall survival was compared between patients receiving propofol or inhaled volatile for anesthesia maintenance. The minimum clinically important difference was defined as a 5-percentage point difference in 5-yr survival. RESULTS: Of 7,571 subjects, 4,519 (59.7%) received an inhaled volatile anesthetic, and 3,052 (40.3%) received propofol for general anesthesia maintenance. The two groups were quite similar in most respects but differed in American Society of Anesthesiologists Physical Status and tumor stage. Propensity score matching was used to address treatment bias. Survival did not differ during follow-up (median, 45 months [interquartile range, 33 to 62 months]) in the full unmatched cohort nor after 1:1 propensity score matching (3,052 matched pairs). The Kaplan-Meier adjusted 5-yr survival rates in the matched cohort were 898 of 3,052, 67.5% (65.6 to 69.3%) for propofol and 852 of 3,052, 68.5% (66.7 to 70.4%) for inhaled volatile general anesthesia, respectively (hazard ratio, 1.05 [95% CI, 0.96 to 1.15]; P = 0.332). A sensitivity analysis restricted to 1,766 propensity score-matched pairs of patients who received only one general anesthetic during the study period did not demonstrate a difference in survival; Kaplan-Meier adjusted 5-yr survival rates were 521 of 1,766, 67.1% (64.7 to 69.7%) and 482 of 1,766, 68.9% (66.5 to 71.4%) for propofol and inhaled volatile general anesthesia, respectively (hazard ratio, 1.09 [95% CI, 0.97 to 1.23]; P = 0.139). CONCLUSIONS: Among patients undergoing bladder cancer surgery under general anesthesia, there was no statistically significant difference in long-term overall survival associated with the choice of propofol or an inhaled volatile maintenance.

Volatile versus Propofol General Anesthesia and Long-term Survival after Breast Cancer Surgery: A National Registry Retrospective Cohort Study.

BACKGROUND: Several retrospective studies using administrative or single-center data have failed to show any difference between general anesthesia using propofol versus inhaled volatiles on long-term survival after breast cancer surgery. Although randomized controlled trials are ongoing, validated data from national clinical registries may advance the reliability of existing knowledge. METHODS: Data on breast cancer surgery performed under general anesthesia between 2013 and 2019 from the Swedish PeriOperative Registry and the National Quality Registry for Breast Cancer were record-linked. Overall survival was compared between patients receiving propofol and patients receiving inhaled volatile for anesthesia maintenance. RESULTS: Of 18,674 subjects, 13,873 patients (74.3%) received propofol and 4,801 (25.7%) received an inhaled volatile for general anesthesia maintenance. The two cohorts differed in most respects. Patients receiving inhaled volatile were older (67 yr vs. 65 yr), sicker (888 [19.0%] American Society of Anesthesiologists status 3 to 5 vs. 1,742 [12.8%]), and the breast cancer to be more advanced. Median follow-up was 33 months (interquartile range, 19 to 48). In the full, unmatched cohort, there was a statistically significantly higher overall survival among patients receiving propofol (13,489 of 13,873 [97.2%]) versus inhaled volatile (4,039 of 4,801 [84.1%]; hazard ratio, 0.80; 95% CI, 0.70 to 0.90; P < 0.001). After 1:1 propensity score matching (4,658 matched pairs), there was no statistically significant difference in overall survival (propofol 4,284 of 4,658 [92.0%]) versus inhaled volatile (4,288 of 4,658 [92.1%]; hazard ratio, 0.98; 95% CI, 0.85 to 1.13; P = 0.756). CONCLUSIONS: Among patients undergoing breast cancer surgery under general anesthesia, no association was observed between the choice of propofol or an inhaled volatile maintenance and overall survival.

Oral nutritional supplement use is weakly associated with increased subjective health-related quality of life in malnourished older adults: a multicentre randomised controlled trial.

Malnutrition is common among older adults in health-care settings and is associated with decreased quality of life (QoL). The present study aimed to investigate the effect on health-related QoL (HRQoL) among older adults after 6 months of treatment with individual dietary advice (DA) and/or oral nutritional supplements (ONS), utilising 409 patients included in a multicentre randomised controlled trial of patients ≥ 65 years old, stratified according to nutrition status (malnourished/at risk of malnutrition), admitted to hospital in Sweden 2010-2014. Patients were randomised into four arms: DA, ONS, DA + ONS or routine care (control). The intervention started at discharge from hospital, with HRQoL measured using European QoL five-dimension, three-level (EQ-5D-3L) and European QoL-visual analogue scale (EQ-VAS) at baseline and at 6-month, 1-year and 3-year follow-ups. Data were analysed using the Kruskal-Wallis test and multiple linear regression. Overall, HRQoL increased from baseline to follow-ups, although the magnitude of change in EQ-5D-3L did not differ significantly between the four arms in any of the nutrition groups. However, a significant difference was observed for change in EQ-VAS from baseline to 6-month follow-up in the malnourished group, with mean changes of 22·4 and -3·4 points for the ONS and control groups, respectively (P = 0·009). In the multiple linear regression analyses, participants in the ONS arm had 27·5, 34·4 and 38·8 points larger increases in EQ-VAS from baseline to the 6-month (P = 0·011), 1-year (P = 0·007) and 3-year (P = 0·032), respectively, follow-ups than the control group. The use of ONS improved subjectively assessed HRQoL in these malnourished older adults.

The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer.

PURPOSE: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). METHODS: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1-T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. RESULTS: Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. CONCLUSIONS: This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. TRIAL REGISTRATION: NCT02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.

Cocreated internet-based stepped care for individuals with cancer and concurrent symptoms of anxiety and depression: Results from the U-CARE AdultCan randomized controlled trial.

OBJECTIVE: The aim was to evaluate the effects of cocreated internet-based stepped care (iCAN-DO) on anxiety, depression, posttraumatic stress, and health-related quality of life (HRQoL) in individuals with cancer and self-reported anxiety and/or depression symptoms, compared with standard care. METHODS: Clinically recruited individuals with breast, colorectal, or prostate cancer underwent online screening with the Hospital Anxiety and Depression Scale (HADS). Those with anxiety and/or depression symptoms (>7 on any of the HADS subscales) were randomized to iCAN-DO or standard care. iCAN-DO comprised psychoeducation and self-care strategies (step 1) and internet-based cognitive behavioral therapy (iCBT, step 2). Data were collected before randomization and at 1, 4, 7, and 10 months and analyzed with intention-to-treat regression analysis and randomization tests. RESULTS: Online screening identified 245 (27%) of 909 individuals who reported anxiety and/or depression symptoms. They were randomized to iCAN-DO (n = 124) or standard care (n = 121). Of them 49% completed the 10-month assessment, and in the iCAN-DO group 85% accessed step 1 and 13% underwent iCBT. iCAN-DO decreased the levels of symptoms of depression (-0.54, 95% confidence interval: -1.08 to -0.01, P < .05) and the proportion of individuals with symptoms of depression (P < .01) at 10 months, compared with standard care, according to HADS. There were no significant effects on anxiety, posttraumatic stress, or HRQoL. CONCLUSION: Internet-based stepped care improves symptoms of depression in individuals with cancer. Further studies are needed to gain knowledge on how to optimize and implement internet-based support in oncology care.

Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia-A retrospective, multicenter, database analysis of 6305 Swedish patients.

BACKGROUND: Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival. METHODS: We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis. RESULTS: The database analysis identified 6305 patients. The 5-year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P = .126). Depending on the statistical adjustment method used, different results were obtained, from a non-significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10-1.95). CONCLUSIONS: It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent.

Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial.

BACKGROUND: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference. METHODS: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1:1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years. DISCUSSION: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors. TRIAL REGISTRATION: NCT 02240472 , retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.

Malnutrition is associated with increased mortality in older adults regardless of the cause of death.

Malnutrition predicts preterm death, but whether this is valid irrespective of the cause of death is unknown. The aim of the present study was to determine whether malnutrition is associated with cause-specific mortality in older adults. This cohort study was conducted in Sweden and included 1767 individuals aged ≥65 years admitted to hospital in 2008-2009. On the basis of the Mini Nutritional Assessment instrument, nutritional risk was assessed as well nourished (score 24-30), at risk of malnutrition (score 17-23·5) or malnourished (score <17). Cause of death was classified according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, into twenty different causes of death. Data were analysed using Cox proportional hazards regression models. At baseline, 55·1 % were at risk of malnutrition, and 9·4 % of the participants were malnourished. During a median follow-up of 5·1 years, 839 participants (47·5 %) died. The multiple Cox regression model identified significant associations (hazard ratio (HR)) between malnutrition and risk of malnutrition, respectively, and death due to neoplasms (HR 2·43 and 1·32); mental or behavioural disorders (HR 5·73 and 5·44); diseases of the nervous (HR 4·39 and 2·08), circulatory (HR 1·95 and 1·57) or respiratory system (HR 2·19 and 1·49); and symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (HR 2·23 and 1·43). Malnutrition and risk of malnutrition are associated with increased mortality regardless of the cause of death, which emphasises the need for nutritional screening to identify older adults who may require nutritional support in order to avoid preterm death.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and breast cancer risk.

The World Cancer Research Fund/American Association for Cancer Research (WCRF/AICR) has published eight nutrition-related recommendations for the prevention of cancer. However, few prospective studies have examined these recommendations by breast cancer hormone receptor subtype and only one case-control study has included the dietary supplements recommendation in their evaluation. We investigated whether adherence to the WCRF/AICR cancer prevention recommendations was associated with breast cancer incidence, overall and by hormone receptor subtype, in the Swedish Mammography Cohort. Among 31,514 primarily postmenopausal women diet and lifestyle factors were assessed with a self-administered food frequency questionnaire. A score was constructed based on adherence to the recommendations for body fatness, physical activity, energy density, plant foods, animal foods, alcoholic drinks and dietary supplements (score range 0-7). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,388 cases of breast cancer were identified. Women who met six to seven recommendations had a 51% decreased risk of breast cancer compared to women meeting only zero to two recommendations (95% CI = 0.35-0.70). The association between each additional recommendation met and breast cancer risk was strongest for the ER-positive/PR-positive subtype (HR = 0.86; 95% CI = 0.79-0.94), while for the ER-negative/PR-negative subtype the individual recommendations regarding plant and animal foods were most strongly associated with reduced risk. Our findings support that adherence to the WCRF/AICR recommendations reduces breast cancer risk in a population of primarily postmenopausal women. Promoting these recommendations to the public could help reduce breast cancer incidence.

The Nordic SentiMag trial: a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies.

The aim of the study is to compare the efficacy of SPIO as a tracer in sentinel node biopsy (SNB) in breast cancer with Tc and patent blue in a multicentre prospective study and perform a meta-analysis of all published studies. It also aims to follow skin discoloration after SPIO injection and describe when and how it resolves. Totally 206 patients with early breast cancer were recruited. Tc and patent blue were administered in standard fashion. Patients were injected with SPIO (Sienna+) preoperatively. SNB was performed and detection rates were recorded for both methods. Skin discoloration was followed and documented postoperatively. Data extraction and subsequent meta-analysis of all previous studies were also performed. SN detection rates were similar between standard technique succeeded and SPIO both per patient (97.1 vs. 97.6 %, p = 0.76) as well as per node (91.3 vs. 93.3 %, p = 0.34), something which was not affected by the presence of malignancy. Concordance rates were also consistently high (98.0 % per patient and 95.9 % per node). Discoloring was present in 35.5 % of patients postoperatively, almost exclusively in breast conservation. It fades slowly and is still detectable in 8.6 % of patients after 15 months. Meta-analysis depicted similar detection rates (p = 0.71) and concordance rates (p = 0.82) per patient. However, it seems that SPIO is characterized by higher nodal retrieval (p < 0.001). SPIO is an effective method for the detection of SN in patients with breast cancer. It is comparable to the standard technique and seems to simplify logistics. Potential skin discoloration is something of consideration in patients planned for breast conservation.

Evaluation of the treatment of chronic chemotherapy-induced peripheral neuropathy using long-wave diathermy and interferential currents: a randomized controlled trial.

PURPOSE: The purpose was to investigate the effects of long-wave diathermy in combination with interferential currents (interferential therapy and long-wave diathermy at high power (ITH)) in comparison with long-wave diathermy at a power below the active treatment dose (long-wave diathermy at low power (LDL), control group) on sensory and motor symptoms in patients with chronic chemotherapy-induced peripheral neuropathy (CIPN) in the lower extremities. METHODS: Sixty-seven patients with chronic CIPN were randomized to 12 weeks of either ITH or LDL. Follow-up assessments were performed after the treatment period and at 37 weeks after randomization. The primary outcome was pain (Numeric Rating Scale (NRS)), and the secondary outcomes were discomfort, nerve symptoms, subjective measurement of dizziness (Dizziness Handicap Inventory), and balance. Differences within and between groups were analyzed. RESULTS: Pain intensity decreased significantly only in the LDL group directly after the treatment period from NRS median 25 to median 12.5 (P = 0.017). At the 37-week follow-up, no changes were detected, irrespective of group (NRS 13 vs. 20, P = 0.885). Discomfort decreased significantly in both groups at both 12 and 37 weeks after the baseline (P < 0.05). Balance disability showed significant declines in both groups at 12 and 37 weeks (P = 0.001/0.025 in the ITH group vs P = 0.001/<0.001 in the LDL group). Balance ability (tightened Romberg test) increased significantly at both 12 and 37 weeks in both groups (P = 0.004/<0.040 in the ITH group) but did not improve in the LDL group at any of the follow-up time points (P = 0.203 vs P = 0.383). The one-legged stance test was unchanged in the ITH group after 12 weeks but improved 37 weeks after baseline (P = 0.03). No significant changes were observed in the LDL group at any of the follow-up time points. CONCLUSION: This study provides no support for the use of a combination of long-wave diathermy and ITH as a treatment option for patients with chronic CIPN. However, the chronic CIPN symptoms decreased with time irrespective of the treatment.

Risk of Complications with Energy-Based Surgical Devices in Thyroid Surgery: A National Multicenter Register Study.

BACKGROUND: Energy-based surgical devices (EBD) combining cutting and coagulation are increasingly used in thyroid surgery. However, there is a lack of information about potential benefits and risk of complications outside controlled trials. The aims of this national multicenter register study were to describe the use of EDB, their potential effect on complication rates, and on operation time. MATERIALS AND METHODS: The Scandinavian Quality Register for Thyroid and Parathyroid surgery includes 35 surgical units in Sweden and covered 88% of the thyroid procedures performed during 2008­2009. The use of the EBD was specifically registered for 12 months, and 1297 patients were included. Surgically related complications and operation time were evaluated. The clamp-and-tie group (C-A-T) constituted the control group for comparison with procedures where EBD was used. RESULTS: The thyroid procedures performed included C-A-T (16.6%), bipolar electrosurgery (ES: 56.5%), electronic vessel sealing (EVS: 12.2%), and ultrasonic dissection (UD: 14.5%). Mean operative time was longer with EVS (p < 0.001) and shorter with UD (p < 0.05) than in the other groups. The bipolar ES group and the EVS group had higher incidence of calcium treatment at discharge and after 6 weeks than the UD group. No significant difference in nerve injury was found between the groups. There was a significant more frequent use of topical hemostatic agents in the EBD group compared to C-A-T. CONCLUSION: In this national multicenter study, the use of UD shortened and EVS increased operating time. There was a higher risk of calcium treatment at discharge and after 6 weeks after use of EVS and bipolar ES than after UD use. There was a significant more frequent use of topical hemostatic agents in the EBD groups compared to C-A-T.

An estrogen-associated dietary pattern and breast cancer risk in the Swedish Mammography Cohort.

High endogenous hormone levels have been associated with breast cancer and dietary factors have the potential to influence breast cancer risk through effects on hormone levels. Dietary patterns derived from reduced rank regression provide a way to identify food groups correlated with hormones and subsequently examine food patterns that may be associated with breast cancer risk. We investigated whether a dietary pattern previously correlated with estradiol and estrone sulfate was associated with breast cancer in the prospective Swedish Mammography Cohort. Among 37,004 primarily postmenopausal women diet was assessed with a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,603 cases of breast cancer were identified. A higher estrogen dietary pattern score was associated with an increased risk of breast cancer. Women in the highest quartile of estrogen pattern score had a 29% (95% CI = 1.08-1.55) increased risk of breast cancer compared to women in the lowest quartile (p(trend) = 0.006). When the association was examined by estrogen-receptor status, it was only significant for those with estrogen-receptor-positive tumors; however, in the competing risk analysis there were no significant differences in the effect estimates by receptor subtype (p(heterogeneity) = 0.65). Our findings suggest that a dietary pattern associated with higher estrogen levels may increase breast cancer risk. However, whether the influence of this dietary pattern is through a direct effect on estrogen levels deserves further study.

A high energy intake from dietary fat among middle-aged and older adults is associated with increased risk of malnutrition 10 years later.

A higher fat content in the diet could be an advantage for preventing malnutrition among older adults. However, there is sparse scientific evidence to determine the optimal fat intake among older adults. This prospective cohort study examined whether a high energy intake of dietary fat among middle-aged and older adults is associated with the risk of malnutrition 10 years later. The study population comprised 725 Swedish men and women aged 53-80 years who had completed a questionnaire about dietary intake and lifestyle factors in 1997 (baseline) and whose nutritional status was assessed when admitted to the hospital in 2008-2009 (follow-up). At the follow-up, 383 (52.8%) participants were identified as being at risk of malnutrition and fifty-two (7.2%) were identified as malnourished. Multinomial logistic regression models were used to analyse the association between previous dietary fat intake and nutritional status later in life. Contrary to what was expected, a high energy intake from total fat, saturated fat and monounsaturated fat among middle-aged and older adults increased the risk of exhibiting malnutrition 10 years later. However, this applied only to individuals with a BMI<25 kg/m² at the baseline. In conclusion, these findings suggest that preventive actions to counteract malnutrition in older adults should focus on limiting the intake of total fat in the diet by reducing consumption of food with a high content of saturated and monounsaturated fat.

Quality assessment of radiotherapy in the prospective randomized SENOMAC trial.

BACKGROUND AND PURPOSE: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. MATERIALS AND METHODS: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail. RESULTS: CRF-data and RT plans agreed in 99.3 % (breast/chest wall) and in 96.6 % of patients (regional RT). Congruence for whether level I was an intended RT target was lower (78 %). In accordance with Danish national guidelines, level I was more often an intended target in the SLN biopsy only arm (N = 334/611, 55 %,) than in the cALND arm (N = 174/565, 31 %,). When an intended target, level I received prescribed dose to 100 % (IQR 98-100 %) of the volume. However, even when not an intended target, full dose was delivered to > 80 % of level I (IQR 75-90 %). The intentional inclusion of level I in the target volume more than doubled the dose received by ≥ 50 % of the humeral head. CONCLUSION: Congruence between CRF data and RT plans was excellent. Level I received a high dose coverage even when not intentionally included in the target. Including level I in target significantly increased dose to the humeral head.

High proliferation is associated with inferior outcome in male breast cancer patients.

Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the luminal subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide male breast cancer into molecular subgroups with different prognoses, the clinical importance of proliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to study proliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset of patients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk for breast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation.

Changes in health-related quality of life by occupational status among women diagnosed with breast cancer--a population-based cohort study.

OBJECTIVE: To investigate whether longitudinal changes in health-related quality of life (HRQoL) among breast cancer patients vary by prediagnosis occupational status or postdiagnosis changes in working time. METHODS: We identified 1573 patients in the Breast Cancer Quality Register of Central Sweden and asked them to participate in a longitudinal questionnaire study. A total of n = 841 women completed three questionnaires within a mean time of 4, 16, and 38 months postdiagnosis. Generalized estimating equation models were used to examine changes in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the Breast Cancer-Specific Quality of Life Questionnaire subscales stratified by prediagnosis occupational status and postdiagnosis changes in working time. RESULTS: Over time, the proportion of employed women reporting good functioning increased more, and the proportion reporting a high level of symptoms decreased more compared with women on sick leave/disability pension and retirement pensioners (p < 0.001). The latter two also showed a worsening in several subscales (p < 0.05). Among employed women, more consistent improvements in role and social functioning were observed among those with an increase/no change in working time than among those who had decreased it or stopped working (p < 0.05). A decrease in the proportion reporting pain was observed among women with an increase/no change in working time compared with women with decreased working time, among whom the proportion reporting pain increased (p = 0.008). CONCLUSIONS: Being employed prediagnosis and resuming work to the same extent as prior to the breast cancer diagnosis are associated with consistent improvements in HRQoL. These results highlight the importance of interventions to improve HRQoL and policies to support return to work following diagnosis.

A randomized controlled trial of support group intervention after breast cancer treatment: results on sick leave, health care utilization and health economy.

BACKGROUND: More than 50% of breast cancer patients are diagnosed before the age of 65. Returning to work after treatment is, therefore, of interest for both the individual and society. The aim was to study the effect of support group intervention on sick leave and health care utilization in economic terms. MATERIAL AND METHODS: Of 382 patients with newly diagnosed breast cancer, 191 + 191 patients were randomized to an intervention group or to a routine control group, respectively. The intervention group received support intervention on a residential basis for one week, followed by four days of follow-up two months later. The support intervention included informative-educational sections, relaxation training, mental visualization and non-verbal communication. Patients answered a questionnaire at baseline, two, six and 12 months about sick leave and health care utilization. RESULTS: There was a trend towards longer sick leave and more health care utilization in the intervention group. The difference in total costs was statistically significantly higher in the intervention group after 12 months (p = 0.0036). CONCLUSION: Costs to society were not reduced with intervention in its present form.

Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact.

BACKGROUND: Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters. MATERIAL AND METHODS: In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event. RESULTS: Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size > 20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition. CONCLUSION: MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.