CD28 expression in sentinel node biopsies from breast cancer patients in comparison with CD3-ζ chain expression

BACKGROUND: Immunosuppression is documented in several malignant diseases, including breast cancer. Subsequently, future therapeutic concepts might include immunological approaches. However, detailed knowledge about tumor immunogenicity and host immunoreactivity, and how to assess these adequately, is still limited. We studied CD28 and CD3-ζ expression in sentinel node biopsies (SNB) from breast cancer patients to analyze tumor-related changes in T cell activity. METHOD: 25 women underwent surgery for primary breast cancer, including SNB. Frozen sections from 21 sentinel nodes could be analyzed with a double-staining technique. CD28 expression was studied in CD4+ and CD8+ T-lymphocyte subsets and compared with CD3-ζ expression in three specified nodal regions. RESULTS: The degree of CD28 expression varied between the different lymph node areas. The lowest degree of CD28 expression was observed in CD4+ T-lymphocytes in the paracortex and germinal centers. Here, a good agreement with CD3-ζ expression was found. A higher CD28 expression was noted in CD4+ T-cells in the primary follicles, where concordance with CD3-ζ expression was weaker. The CD8+ T-lymphocyte subset displayed generally a higher degree of CD28 expression than the CD4+ subset. CONCLUSION: Sentinel lymph nodes from breast cancer patients displayed local immunosuppression of varying extent. In the areas with the lowest degree of CD28 expression an accordingly low CD3-ζ expression was found. The SNB might prove an important diagnostic tool for the evaluation of interactions between tumor and the host immune system, helping to select patients who might benefit from adjuvant immunotherapy

Knee arthroscopies: who gets them, what does the radiologist report, and what does the surgeon find?

Background and purpose - Several randomized controlled trials have not shown any added benefit of arthroscopy over placebo surgery or physiotherapy in middle-aged patients with knee symptoms without trauma. We studied the characteristics of the knee arthroscopies performed in southern Sweden. Patients and methods - From the orthopedic surgical records from 2007-2009 in the Skåne region of Sweden (with a population of 1.2 million), we retrieved ICD-10 diagnostic codes and selected all 4,096 arthroscopies that were diagnosed peroperatively with code M23.2 (derangement of meniscus due to old tear or injury) or code M17 (knee osteoarthritis). We extracted information on cartilage and meniscus status at arthroscopy, and we also randomly sampled 502 of these patients from the regional archive of radiology and analyzed the preoperative prevalence of radiographic or magnetic resonance imaging (MRI)-defined osteoarthritis. Results - 2,165 (53%) of the 4,096 arthroscopies had the diagnostic code M23.2 or M17. In this subgroup, 1,375 cases (64%) had typical findings consistent with degenerative meniscal tear (i.e. that correspond to a degenerative meniscal tear in at least a third of all arthroscopies). Of the randomly sampled patients, the preoperative prevalence of radiological knee osteoarthritis was 46%. Interpretation - There is a discrepancy between evidence-based medicine treatment guidelines and clinical practice regarding the amount of knee arthroscopies performed in patients with symptoms of degenerative knee disease

Metaplastic Carcinoma of the Breast with Neuroectodermal Stromal Component

A unique case of metaplastic breast carcinoma with an epithelial component showing tumoral necrosis and neuroectodermal stromal component is described. The tumor grew rapidly and measured 9 cm at the time of diagnosis. No lymph node metastases were present. The disease progressed rapidly and the patient died two years after the diagnosis from a hemorrhage caused by brain metastases. The morphology and phenotype of the tumor are described in detail and the differential diagnostic options are discussed

Differences in Management of Older Women Influence Breast Cancer Survival: Results from a Population-Based Database in Sweden

BACKGROUND: Several reports have shown that less aggressive patterns of diagnostic activity and care are provided to elderly breast carcinoma patients. We sought to investigate whether differences in the management of older women with breast cancer are associated with survival. METHODS AND FINDINGS: In an observational study using a population-based clinical breast cancer register of one health-care region in Sweden, we identified 9,059 women aged 50–84 y diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative survival ratio was estimated for patients classified by age group, diagnostic activity, tumor characteristics, and treatment. The 5-y relative survival for breast cancer patients was lower (up to 13%) in women 70–84 y of age compared to women aged 50–69 y, and the difference was most pronounced in stage IIB–III and in the unstaged. Significant differences in disease management were found, as older women had larger tumors, had fewer nodes examined, and did not receive treatment by radiotherapy or by chemotherapy as often as the younger women. Adjustment for diagnostic activity, tumor characteristics, and treatment diminished the relative excess mortality in stages III and in the unstaged, whereas the excess mortality was only marginally affected in stage IIB. CONCLUSIONS: Less diagnostic activity, less aggressive treatment, and later diagnosis in older women are associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone

Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial

Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQC30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.Peer reviewe

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: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015Peer reviewe

Breast Cancer, Sickness Absence, Income and Marital Status. A Study on Life Situation 1 Year Prior Diagnosis Compared to 3 and 5 Years after Diagnosis

Background: Improved cancer survival poses important questions about future life conditions of the survivor. We examined the possible influence of a breast cancer diagnosis on subsequent working and marital status, sickness absence and income. Materials: We conducted a matched cohort study including 4,761 women 40–59 years of age and registered with primary breast cancer in a Swedish population-based clinical register during 1993–2003, and 2,3805 women without breast cancer. Information on socioeconomic standing was obtained from a social database 1 year prior and 3 and 5 years following the diagnosis. In Conditional Poisson Regression models, risk ratios (RRs) and 95 % confidence intervals (CIs) were estimated to assess the impact of a breast cancer diagnosis. Findings: Three years after diagnosis, women who had had breast cancer more often had received sickness benefits (RR = 1.49, 95 % CI 1.40–1.58) or disability pension (RR = 1.47, 95 % CI 1.37–1.58) than had women without breast cancer. W