Background

It is debated if all breast cancer (BC) patients with sentinel lymph node metastasis need axillary lymph node dissection (ALND). Based on clinical and biological factors, we explore a statistical model for predicting non sentinel node metastasis (non-SNm) in patients with positive SN (SN+).

Methods

We obtained data on patients from the Swedish National Quality Register for BC patients operated Jan 2008 - May 2012. Pearson´s chi-squared test was performed to compare clinical data with presence of non-SNm. The risk of non-SNm, estimated as odds ratio (OR), was calculated with multivariable logistic regression analysis and the results were visualized with a nomogram. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory ability of the regression model (Prisk) in predicting non-SNm.

Results

Out of 5382 patients with SN+, 3181 had macro metastases at sentinel node biopsy and were treated with ALND. The non-SNm was statistically significant correlated to the proportion of SN+ (OR increased from 1.41 to 3.75 with raised proportion, p<0.001), tumor size (OR= 1.70, p<0.001), LVI-lymphovascular infiltration (OR= 1.63, p<0.001), HER2 expression (OR= 1.49, p=0.004) and multifocality (OR= 1.28, p=0.04). A cut-off value of 0.3 for Prisk based on the logistic regression model, yielded a sensitivity of 83.2% and specificity of 34.7 % in predicting non-SNm. The results were visualized with a nomogram where the proportion of SN+ was the most important factor.

Conclusion

In this study we present a statistical score encompassing BC biology with good sensitivity and acceptable specificity that may be used in predicting non-SNm as a complement to traditional staging system used in clinical assessment of BC.

Background: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with &gt;10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. Purpose: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. Material and methods: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. Results: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. Conclusions: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background The implementation of screening programmes in Sweden during the mid-1990s increased the number of small node-negative breast cancers. In this era before staging by sentinel node biopsy, routine axillary dissection for staging of early breast cancer was questioned owing to the increased morbidity and lack of perceived benefit. The long-term risk of axillary recurrence when axillary staging is omitted remains unclear. Methods This prospective observational multicentre cohort study included Swedish women diagnosed with breast cancer between 1997 and 2002. The patients had clinically node-negative, pT1a-b, grade I-II tumours. No axillary staging or dissection was performed. The primary outcome was ipsilateral axillary recurrence and survival. Results A total of 1543 patients were included. Breast-conserving surgery (BCS) was performed in 94 center dot 0 per cent and the rest underwent mastectomy. After surgery, 58 center dot 1 per cent of the women received adjuvant radiotherapy, 11 center dot 9 per cent adjuvant endocrine therapy and 31 center dot 5 per cent did not receive any adjuvant treatment. After a median follow-up of 15 center dot 5 years, 6 center dot 4 per cent developed contralateral breast cancer and 16 center dot 5 per cent experienced a recurrence. The first recurrence was local in 116, regional in 47 and distant in 59 patients. The breast cancer-specific survival rate was 93 center dot 7 per cent after 15 years. There were no differences in overall or breast cancer-specific survival between patients who received adjuvant radiotherapy and those who did not. Only 3 center dot 0 per cent of patients had an axillary recurrence, which was isolated in only 1 center dot 0 per cent. Conclusion Axillary surgery can safely be omitted in patients with low-grade, T1a-b, cN0 breast cancers. This large prospective cohort with 15-year follow-up had a very low incidence of axillary recurrences and high breast cancer-specific survival rate.

Background: During the recent decades, breast cancer survival has gradually improved but there is limited knowledge on the improvement in population-based studies of patients diagnosed with different stages of the disease and in different age groups.Patients and methods: In two Swedish health care regions a total of 42,220 female breast cancer patients below 90years of age were diagnosed between 1989 and 2013. They were treated and followed according to national and regional guidelines and formed a population-based cohort.Results: Using patients diagnosed in 1989-1993 as a reference to the relative risk, 5-year mortality decreased with 49% for patients diagnosed at the end of the observation period (CI 95% 45-58). The mortality tended to decrease for patients with all stages of breast cancer and test for trend resulted in a statistically significant improvement over time in 5-year relative survival in stage III and IV and in 10-year survival in stage I and III. For each operable stage of disease, patients aged below 40years or more than 70years when diagnosed tended to have less favorable survival than patients diagnosed between 40-69years of age. Test for trend resulted in statistically significant improvements over time for patients diagnosed at ages below 40, 40-54 and 54-69, but less marked improvements for patients older than 70 when diagnosed.Conclusions: During the period 1989-2013 the relative risk of 5-year mortality decreased with 49%. Improvements were seen in all age groups but were unevenly distributed between stages and age groups pointing to the need for further improvements for younger and elderly patients.

Background: In published radiotherapy trials, the failure rate in the control arm among patients with one to three positive nodes is high compared with that seen with modern adjuvant treatments. Therefore, the generalizability of the results has been questioned. The aim of the present study was to compare relative survival in breast cancer patients between two Swedish regions with screening mammography programs and adjuvant treatment guidelines similar with the exception of the indication of radiotherapy for patients with one to three positive nodes. Patients and methods: Between 1989 and 2006, breast cancer patients were managed very similarly in the west and southeast regions, except for indication for postoperative radiotherapy. In patients with one to three positive nodes, post-mastectomy radiotherapy was generally given in the southeast region (89% of all cases) and generally not given in the west region (15% of all cases). For patients with one to three positive nodes who underwent breast-conserving surgery, patients in the west region had breast radiotherapy only, while patients in the southeast region had both breast and lymph nodes irradiated. Results: The 10-year relative survival for patients with one to three positive lymph nodes was 78% in the west region and 77% in the southeast region (P = 0.12). Separate analyses depending on type of surgery, as well as number of examined nodes, also revealed similar relative survival. Conclusion: Locoregional postoperative radiotherapy has well-known side-effects, but in this population-based study, there was little or no influence of this type of radiotherapy on survival when one to three lymph nodes were involved.

Purpose Four randomized studies show that adjuvant radiotherapy (RT) lowers the risk of subsequent ipsilateral breast events (IBEs) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) by approximately 50% after 10 to 15 years. We present 20 years of follow-up data for the SweDCIS trial. Patients and Methods Between 1987 and 1999 1,046 women were randomly assigned to RT or not after BCS for primary DCIS. Results up to 2005 have been published, and we now add another 7 years of follow-up. All breast cancer events and causes of death were registered. Results There were 129 in situ and 129 invasive IBEs. Absolute risk reduction in the RT arm was 12.0% at 20 years (95% CI, 6.5 to 17.7), with a relative risk reduction of 37.5%. Absolute reduction was 10.0% (95% CI, 6.0 to 14.0) for in situ and 2.0% (95% CI, -3.0 to 7.0) for invasive IBEs. There was a nonstatistically significantly increased number of contralateral events in the RT arm (67 v 48 events; hazard ratio, 1.38; 95% CI, 0.95 to 2.00). Breast cancer-specific death and overall survival were not influenced. Younger women experienced a relatively higher risk of invasive IBE and lower effect of RT. The hazard over time looked different for in situ and invasive IBEs. Conclusion Use of adjuvant RT is supported by 20-year follow-up. Modest protection against invasive recurrences and a possible increase in contralateral cancers still call for a need to find groups of patients for whom RT could be avoided or mastectomy with breast reconstruction is indicated.

Background: According to current guidelines, patients with primary breast cancer and 1-3 lymph node metastases will in general be offered adjuvant chemotherapy. less thanbrgreater than less thanbrgreater thanAim: Our objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely. less thanbrgreater than less thanbrgreater thanMaterial and methods: Tumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I-III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined. less thanbrgreater than less thanbrgreater thanResults: A wide range of ccCK18 protein levels was found, median 9.97, range 0.0-87.3 pg/mu gDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p andlt; 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1-3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Coxs proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22-0.98), p = 0.043), and BCS (HR = 0.39 (0.16-1.00), p = 0.049), respectively. less thanbrgreater than less thanbrgreater thanConclusion: By use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1-3 lymph node metastases with good outcome following adjuvant tamoxifen was identified; this group could possibly be spared adjuvant chemotherapy.

Background: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. less thanbrgreater than less thanbrgreater thanMethods: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. less thanbrgreater than less thanbrgreater thanResults: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (Cl) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% Cl 2.20-140). less thanbrgreater than less thanbrgreater thanConclusion: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.

Selective venous sampling (SVS) helps to interpret imaging results in patients with persistent primary hyperparathyroidism (pHPT). However, one of the drawbacks of conventional SVS may be low "spatial resolution", depending on the sample size. We modified SVS in the following way: first, patients underwent conventional SVS with up to 11 parathyroid hormone (PTH) samples taken. The quickPTH assay was used to measure PTH levels. The patients subsequently underwent super-selective venous sampling (super-SVS) in the region with the highest quickPTH level in the same session. The subjects were five consecutive patients with persistent pHPT investigated by various imaging techniques, none of which was considered conclusive. Therefore, all five patients underwent super-SVS, which was done successfully in four. Re-evaluation of the imaging results of these four patients resulted in localization of the parathyroid adenoma. Curative surgery was performed successfully in all four patients during the study period. Super-SVS increases the "spatial resolution" of conventional SVS and may have advantages when imaging results of patients with persistent pHPT are interpreted. Its true value must be analyzed in larger studies.

Purpose. Continuous minor steps of improvement in the management of breast cancer have resulted in decreased mortality rates during the last decades. The aim of this study was to compare the clinical outcome of patients with stage I breast cancer diagnosed during two time periods that differed with respect to adjuvant systemic therapy. Material and methods. The studied population consisted of all women 60 years of age, who were diagnosed breast cancer stage I between 1986 and 1999 in south-east Sweden, a total of 1 407 cases. The cohort was divided into two groups based on the management programmes of 1986 and 1992, hereafter referred to as Period 1 and Period 2. Before 1992 the only adjuvant systemic therapy recommended was tamoxifen for hormone receptor positive patients aged 50 years or older. During Period 2 the use of adjuvant treatment was extended to younger patients at high risk, identified by a high tumour S-phase fraction, with either hormonal or cytotoxic treatment. Results. The estimated distant recurrence-free survival rate was significantly higher during Period 2 than during Period 1 (p = 0.008). Subgroup analysis showed that the most evident reduction of distant recurrence risk was among hormone receptor-negative patients (HR = 0.58, 95% CI 0.31-1.09, p = 0.09) and among patients with a high tumour S-phase fraction (HR = 0.53, 0.30-0.93, p = 0.028). The risk reduction between the periods was still statistically significant in multivariate analysis when adjusting for different tumour characteristics and treatment modalities, indicating an influence of other factors not controlled for. One such factor may be the duration of tamoxifen treatment, which likely was more frequently five years during Period 2 than during Period 1. Conclusions. We conclude that the causes of the increase in distant recurrence free survival for women with breast cancer stage I are complex. The results support though that high-risk subgroups of stage I breast cancer patients did benefit from increased use of systemic therapy as a consequence of an updated management programme.