Validation and Clinical Utility of a Prediction Model for the Risk of Upstaging to Invasive Breast Cancer After a Biopsy Diagnosis Ductal Carcinoma In Situ.

BACKGROUND: This study aimed to validate the DCIS-upstage model, a previously developed model to predict the risk of upstaging to invasive breast cancer in patients with biopsy-proven ductal carcinoma in situ (DCIS) in a more recent cohort and to assess the model's clinical utility. METHODS: The model was validated in a registry cohort (n = 2269) and in an institution cohort (n = 302). A calibration plot was made, followed by a decision curve analysis (DCA). The model's area under the curve (AUC) was compared with the AUC of another published model and with the AUCs of new models using the risk factors of the DCIS-upstage model and additional risk factors. RESULTS: The DCIS-upstage model had an AUC of 0.67 at development; in the validation, the AUC was 0.65 in the registry cohort and 0.73 in the institution cohort. The DCA showed that the model has clinical utility. The other published model had an AUC of 0.66 in the institution cohort. Adding risk factors to the DCIS-upstage model slightly increased the AUC. CONCLUSIONS: The DCIS-upstage prediction model is valid in other cohorts. The model has clinical utility and may be used to select patients with biopsy-proven DCIS for sentinel lymph node biopsy.

What affects women's decision-making on breast reconstruction after mastectomy for breast cancer?

PURPOSE: To establish the breast reconstruction rate in a large Dutch teaching hospital, and to gain insight into the motives of women to opt for or reject post-mastectomy breast reconstruction. METHODS: In a retrospective, cross-sectional study, all consecutive patients who underwent mastectomy for invasive breast cancer or ductal carcinoma in situ (DCIS) were identified and categorized into two groups based on subsequent breast reconstruction or not. Patient-reported outcomes were assessed with the validated Breast-Q and a short survey about the decision-making process in breast reconstruction. These outcomes were compared between the two groups using univariable analyses, multivariable logistic regression, and multiple linear regression analyses. The Breast-Q scores were also compared to Dutch normative values. RESULTS: A total of 319 patients were identified of whom 68% had no breast reconstruction. Of the 102 patients with breast reconstruction, the majority (93%) received immediate, instead of delayed breast reconstruction. The survey was completed by 155 (49%) patients. The non-reconstruction group, on average, reported significantly poorer psychosocial well-being, compared to the reconstruction group as well as compared to the normative data. However, the majority of the non-reconstruction group (83%) stated that they had no desire for breast reconstruction. In both groups, most patients stated that the provided information was sufficient. CONCLUSION: Patients have personal motives to opt for or reject breast reconstruction. It seemed that patients differ in their rating of values that affect their decision since the same arguments were used to opt for or reject reconstruction. Notably, patients were well-informed in their decision making.

A low risk of recurrence after breast-conserving surgery for DCIS: A single-institution experience.

BACKGROUND: Previously published studies report up to 30% recurrence rates after DCIS, so it would be desirable to identify those women at risk for recurrence and adapt adjuvant management. This study aimed to identify the locoregional recurrence rate after breast conserving surgery (BCS) for DCIS, and to evaluate the possible role of immunohistochemical (IHC) staining in predicting the risk of recurrence. PATIENTS AND METHODS: In a retrospective cohort study, patients who underwent BCS for pure DCIS were identified. Data on well-established clinical-pathological risk factors and development of locoregional recurrence was gathered from patient files. In addition, IHC stains of ER, PR, HER2, p53, and ki67 were performed on original tumor samples. Univariable Cox regression analyses were performed to identify possible risk factors for locoregional recurrence. RESULTS: 190 patients were included. At a median follow-up time of 12.8 years fifteen (8%) patients developed locoregional recurrence: 7 invasive cancer and 8 DCIS. These recurrences were diagnosed within a range of 1.7 to 19.6 years after the initial diagnosis. Univariable Cox regression analysis did only show a significant association between p53 and locoregional recurrence. Our re-excision rate to obtain free margins was 30.5%, and 90% received radiotherapy. Endocrine treatment was not used. CONCLUSIONS: At 12.8 years follow-up, patients with DCIS treated with BCS have a very low locoregional recurrence of 8%. Although we could demonstrate that increased p53 expression is a risk factor for locoregional recurrence, we think this is of little clinical value in our population with such a low recurrence rate. MICROABSTRACT: With a published recurrence rate up to 30% after DCIS, it would be desirable to identify those at risk to adapt treatment and follow-up. We aimed to evaluate the role of immunohistochemical staining to determine the risk of locoregional recurrence, in addition to established clinical and pathological risk factors. At a median follow-up of 12.8 years, we found a locoregional recurrence rate of 8%. Increased expression of p53 is associated with an increased risk of locoregional recurrence.

Predicting Lymph Node Metastases in Patients with Biopsy-Proven Ductal Carcinoma In Situ of the Breast: Development and Validation of the DCIS-met Model.

PURPOSE: In patients with a biopsy-proven ductal carcinoma in situ (DCIS), axillary staging is frequently performed, but in hindsight often turns out to be superfluous. The aim of this observational study was to develop a prediction model for risk of lymph node metastasis in patients with a biopsy-proven DCIS. METHODS: Data were received from the Dutch Pathology Databank and the Netherlands Cancer Registry. The population-based cohort consisted of all biopsy-proven DCIS patients diagnosed in the Netherlands in 2011 and 2012. The prediction model was evaluated with the area under the curve (AUC) of the receiver operating characteristic, and a calibration plot and a decision curve analysis and was validated in a Dutch cohort of patients diagnosed in the period 2016-2019. RESULTS: Of 2892 biopsy-proven DCIS patients, 127 had metastasis (4.4%). Risk factors were younger age (OR = 0.97, 95% CI 0.95-0.99), DCIS not detected by screening (OR = 1.55, 95% CI 1.01-2.38), suspected invasive component at biopsy (OR = 1.86, 95% CI 1.01-3.41), palpable tumour (OR = 2.06, 95% CI 1.34-3.18), BI-RADS score 5 (OR = 2.41, 95% CI 1.53-3.78), intermediate-grade DCIS (OR = 3.01, 95% CI 1.27-7.15) and high-grade DCIS (OR = 3.20, 95% CI 1.36-7.54). For 24% (n = 708) of the patients, the predicted risk of lymph node metastasis was above 5%. Based on the decision curve analysis, the model had a net benefit for a predicted risk below 25%. The AUC was 0.745. Of the 2269 patients in the validation cohort, 53 (2.2%) had metastasis and the AUC was 0.741. CONCLUSIONS: This DCIS-met model can support clinical decisions on axillary staging in patients with biopsy-proven DCIS.

Gastric metastasis of breast cancer: A frequent mimicker of primary gastric cancer in breast cancer patients.

Gastric metastasis of breast cancer is a known mimicker of primary gastric cancer. This paper demonstrates that in patients with a history of breast cancer, gastric metastasis and primary gastric cancer are equally likely.

Longitudinal Serum Protein Analysis of Women with a High Risk of Developing Breast Cancer Reveals Large Interpatient Versus Small Intrapatient Variations: First Results from the TESTBREAST Study.

The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection.

Diagnostic Accuracy of Radioactive Iodine Seed Placement in the Axilla With Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer.

Importance: Several less-invasive staging procedures have been proposed to replace axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) in patients with initially clinically node-positive (cN+) breast cancer, but these procedures may fail to detect residual disease. Owing to the lack of high-level evidence, it is not yet clear which procedure is most optimal to replace ALND. Objective: To determine the diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS), a targeted axillary dissection procedure. Design, Setting, and Participants: This was a prospective, multicenter, noninferiority, diagnostic accuracy trial conducted from March 1, 2017, to December 31, 2019. Patients were included within 14 institutions (general, teaching, and academic) throughout the Netherlands. Patients with breast cancer clinical tumor categories 1 through 4 (cT1-4; tumor diameter <2 cm and up to >5 cm or extension to the chest wall or skin) and pathologically proven positive axillary lymph nodes (ie, clinical node categories cN1, metastases to movable ipsilateral level I and/or level II axillary nodes; cN2, metastases to fixed or matted ipsilateral level I and/or level II axillary nodes; cN3b, metastases to ipsilateral level I and/or level II axillary nodes with metastases to internal mammary nodes) who were treated with NAC were eligible for inclusion. Data were analyzed from July 2020 to December 2021. Intervention: Pre-NAC, the marking of a pathologically confirmed positive axillary lymph node with radioactive iodine seed (MARI) procedure, was performed and after NAC, sentinel lymph node biopsy (SLNB) combined with excision of the marked lymph node (ie, RISAS procedure) was performed, followed by ALND. Main Outcomes and Measures: The identification rate, false-negative rate (FNR), and negative predictive value (NPV) were calculated for all 3 procedures: RISAS, SLNB, and MARI. The noninferiority margin of the observed FNR was 6.25% for the RISAS procedure. Results: A total of 212 patients (median [range] age, 52 [22-77] years) who had cN+ breast cancer underwent the RISAS procedure and ALND. The identification rate of the RISAS procedure was 98.2% (223 of 227). The identification rates of SLNB and MARI were 86.4% (197 of 228) and 94.1% (224 of 238), respectively. FNR of the RISAS procedure was 3.5% (5 of 144; 90% CI, 1.38-7.16), and NPV was 92.8% (64 of 69; 90% CI, 85.37-97.10), compared with an FNR of 17.9% (22 of 123; 90% CI, 12.4%-24.5%) and NPV of 72.8% (59 of 81; 90% CI, 63.5%-80.8%) for SLNB and an FNR of 7.0% (10 of 143; 90% CI, 3.8%-11.6%) and NPV of 86.3% (63 of 73; 90% CI, 77.9%-92.4%) for the MARI procedure. In a subgroup of 174 patients in whom SLNB and the MARI procedure were successful and ALND was performed, FNR of the RISAS procedure was 2.5% (3 of 118; 90% CI, 0.7%-6.4%), compared with 18.6% (22 of 118; 90% CI, 13.0%-25.5%) for SLNB (P < .001) and 6.8% (8 of 118; 90% CI, 3.4%-11.9%) for the MARI procedure (P = .03). Conclusions and Relevance: Results of this diagnostic study suggest that the RISAS procedure was the most feasible and accurate less-invasive procedure for axillary staging after NAC in patients with cN+ breast cancer.

Surgeons' preferences for using sentinel lymph node biopsy in patients with ductal carcinoma in situ.

BACKGROUND: There is a large variation between Dutch hospitals in the use of Sentinel Lymph Node Biopsy (SLNB) in patients with a biopsy diagnosis of Ductal Carcinoma in Situ. The aim of our study was to investigate whether this variation might be explained by preferences of surgeons, organisational factors or the influence of patients preferences. METHODS: A cross-sectional web survey was conducted among 260 Dutch oncological/breast surgeons. Preferences of surgeons and the influence of the patients' preferences were determined by means of best-worst scaling (BWS) of profile case scenarios and by ranking risk factors. The survey also explored organisational questions, the reported use of diagnostic techniques and influences on the decision. RESULTS: The BWS scenarios were completed by 57 surgeons. The most important reasons for performing SLNB were a suspected invasive component and DCIS grade 3. In the ranking, these were also the first and second most important factor, followed by the size of the lesion and a mass on mammogram. In 58% to 70% of the scenarios, the surgeons would not change their decisions on the use of SLNB if the patient's chose differed. No organisational factor was significantly associated with the reported use of SLNB. CONCLUSION: The inter-hospital variation in the use of SLNB could not be attributed to organisational factors or surgeons' preferences for risk factors. The risk factors that most surgeons reported as reasons for performing SLNB are consistent with the factors described in the Dutch treatment guideline for the use of SLNB.

Trends in incidence, treatment, survival and subsequent breast cancer in lobular carcinoma in situ in the Netherlands: A population-based analysis.

PURPOSE: We analysed incidence, treatment, survival, occurrence of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) after lobular carcinoma in situ (LCIS) in the Netherlands. METHODS: All women diagnosed with classic LCIS between 1989 and 2017 were identified from the Netherlands Cancer Registry. We calculated overall (OS), relative survival (RS) and cumulative incidence functions (CIF, accounting for competing risks) of mortality, DCIS and IBC. For IBC, standardised incidence ratios (SIR) of IBC were calculated. Analyses were stratified for surgical treatment. RESULTS: We included 1890 patients. Median age was 51 years. Median follow-up was 8.5 years. In 1989-2017, LCIS incidence increased from 41 to 124, surgical treatment decreased from 100% to 41.1 % - mostly BCS. 10-year OS and 20-year RS exceeded 90 % in all subgroups. Overall, 48 (2.5 %) and 270 (14.3 %) patients were diagnosed with DCIS and IBC. IBCs were mostly early-stage. After mastectomy, 13 of 14 IBCs presented contralaterally. In the other groups, 64.8-70.9 % of IBCs presented ipsilaterally, 34.5-53.9 % of these were lobular. The SIR of ipsilateral IBC was highest after no surgery (6.9, 95%CI:4.9-9.4), lowest after mastectomy (0.2, 95%CI:0.4-0.8). CONCLUSION: LCIS incidence increased, surgical treatment decreased. The low mortality risks support consideration of active surveillance. However, the increased IBC incidence suggests careful monitoring.

Ten years follow-up of histologically benign calcifications in the breast after vacuum-assisted stereotactic biopsy (VASB): Is additional mammographic follow-up warranted?

OBJECTIVE: This study assessed the short-term and the long-term breast cancer rate in patients with benign histopathologic results after a vacuum-assisted stereotactic biopsy (VASB) for calcifications. METHODS: In a retrospective cohort study, all consecutive patients who had a benign diagnosis after VASB to analyze breast calcifications. Data of breast cancer development at short-term (four years) and long-term follow-up was gathered. Breast cancer rates in our cohort were compared to the breast cancer incidence in the general population. RESULTS: Of 1376 patients who underwent VASB to analyze breast calcifications, 823 had a benign histopathologic diagnosis. During short-term follow-up, eight patients developed breast cancer. During the mean long-term follow-up period of 9.3 ± 3.1 years, 22 patients were diagnosed with ipsilateral breast cancer. The incidence rate of breast cancer after benign biopsy was comparable to the rate in the general population. CONCLUSION: In patients with VASB-confirmed benign calcifications of the breast, we found no excess incidence of ipsilateral breast cancer during ten years follow-up. Therefore, in patients with an increased risk of breast cancer (due to a history of breast cancer or familial risk) annual mammography should be sufficient. Patients with a population-based risk may be monitored via biennial mammography by the national screening program. More frequent screening would provide no benefit.

Preoperative breast MRI in management of patients with needle biopsy-proven ductal carcinoma in situ (DCIS).

BACKGROUND: In 20-25% of patients with biopsy-proven DCIS underestimation occurs. Sentinel lymph node biopsy (SLNB) is offered to patients with biopsy-proven ductal carcinoma in situ (DCIS) and a high risk of occult invasive cancer. However, assessment of high risk is controversial. We aimed to improve selection of patients for SLNB with preoperative breast magnetic resonance imaging (MRI). METHODS: In this prospective observational study, MRI was offered to all subsequent patients with a biopsy-proven DCIS admitted to a large Dutch teaching hospital between April 2012 and March 2017. MRI images were analysed for signs of invasive cancer and the results were compared with the pathologic results after surgical treatment. The diagnostic accuracy of additional MRI in detecting occult invasive cancer was determined. RESULTS: Of 211 patients eligible for additional MRI analysis, 149 underwent breast MRI. The majority (67%) received breast-conserving therapy, and the underestimation rate was 20%. Subsequent to MRI analysis, 20 additional invasive diagnostic procedures were performed. Occult invasive cancer was suspected on MRI in 46 patients (31%) and was confirmed in 18 (12%). In this study, breast MRI had a sensitivity of 67%, a specificity of 77%, and a true negative rate of 91%. CONCLUSION: Preoperative breast MRI cannot reliably predict the presence of invasive cancer in patients with biopsy proven DCIS. Therefore, it cannot be used to in the selection of patients for a SLNB.

A patient- and assessor-blinded randomized controlled trial of axillary reverse mapping (ARM) in patients with early breast cancer.

BACKGROUND: Axillary lymph node dissection (ALND) in breast cancer patients is infamous for its accompanying morbidity. Selective preservation of upper extremity lymphatic drainage and accompanying lymph nodes crossing the axillary basin - currently resected during a standard ALND - has been proposed as a valuable surgical refinement. METHODS: Peroperative Axillary Reversed Mapping (ARM) was used for selective preservation of upper extremity lymphatic drainage. A multicentre patient- and assessor-blinded randomized study was performed in clinical node negative, sentinel node positive early breast cancer patients. Patients were randomized to undergo either standard-ALND or ARM-ALND. Primary outcome was the presence of surgery-related lymphedema at six, 12 and 24 months post-operatively. Secondary outcomes included patient reported and objective signs and symptoms of lymphedema, pain, paraesthesia, numbness, loss of shoulder mobility, quality of life and axillary recurrence risk. RESULTS: No significant differences were found between both groups using the water displacement method with respect to measured lymphedema. ARM-ALND resulted in less reported complaints of lymphedema at six, 12 and 24 months postoperatively (p < 0.05). No axillary recurrence was found in both groups. CONCLUSIONS: In contrast to results of volumetric measurement, patient reported outcomes support selective sparing of the upper extremity lymphatic drainage using ARM as valuable surgical refinement in case of ALND in clinically node negative, sentinel node positive early breast cancer. If completion ALND in clinically node negative, sentinel node positive early breast cancer is considered, selective sparing of upper extremity axillary lymphatics by implementing ARM should be carried out in order to reduce morbidity.

Health care use and remaining needs for support among women with breast cancer in the first 15 months after diagnosis: the role of the GP.

BACKGROUND: The number of women with breast cancer in general practice is rising. To address their needs and wishes for a referral, GPs might benefit from more insight into women's health care practices and need for additional support. OBJECTIVE: To examine the prevalence of health care use and remaining needs among women with breast cancer in the first 15 months after diagnosis. METHODS: In this multicentre, prospective, observational study women with breast cancer completed a questionnaire at 6 and 15 months post-diagnosis. Medical data were retrieved through chart reviews. The prevalence of types of health care used and remaining needs related to medical, psychosocial, paramedical and supplementary service care (such as home care), was examined with descriptive analyses. RESULTS: Seven hundred forty-six women completed both questionnaires. At both assessments patients reported that they had most frequent contact with medical and paramedical providers, independent of types of treatment received. Three to fifteen percent of the patients expressed a need for more support. Prominent needs included a wish for more frequent contact with a physiotherapist, a clinical geneticist and a psychologist. Patients also wanted more help for chores around the house, particularly in the early post-treatment phase. CONCLUSION: A small but relevant percentage of women with breast cancer report having unmet needs. GPs may need to be particularly watchful of their need for more support from specific providers. Future research into the necessity of structural needs assessment among cancer patients in general practice is warranted.

Risk factors of unmet needs among women with breast cancer in the post-treatment phase.

OBJECTIVE: Unmet health care needs require additional care resources to achieve optimal patient well-being. In this nationwide study we examined associations between a number of risk factors and unmet needs after treatment among women with breast cancer, while taking into account their health care practices. We expected that more care use would be associated with lower levels of unmet needs. METHODS: A multicenter, prospective, observational design was employed. Women with primary breast cancer completed questionnaires 6 and 15 months post-diagnosis. Medical data were retrieved from medical records. Direct and indirect associations between sociodemographic and clinical risk factors, distress, care use, and unmet needs were investigated with structural equation modeling. RESULTS: Seven hundred forty-six participants completed both questionnaires (response rate 73.7%). The care services received were not negatively associated with the reported levels of unmet needs after treatment. Comorbidity was associated with higher physical and daily living needs. Higher age was associated with higher health system-related and informational needs. Having had chemotherapy and a mastectomy were associated with higher sexuality needs and breast cancer-specific issues, respectively. A higher level of distress was associated with higher levels of unmet need in all domains. CONCLUSIONS: Clinicians may use these results to timely identify which women are at risk of developing specific unmet needs after treatment. Evidence-based, cost-effective (online) interventions that target distress, the most influential risk factor, should be further implemented and disseminated among patients and clinicians.

A prediction model for underestimation of invasive breast cancer after a biopsy diagnosis of ductal carcinoma in situ: based on 2892 biopsies and 589 invasive cancers.

BACKGROUND: Patients with a biopsy diagnosis of ductal carcinoma in situ (DCIS) might be diagnosed with invasive breast cancer at excision, a phenomenon known as underestimation. Patients with DCIS are treated based on the risk of underestimation or progression to invasive cancer. The aim of our study was to expand the knowledge on underestimation and to develop a prediction model. METHODS: Population-based data were retrieved from the Dutch Pathology Registry and the Netherlands Cancer Registry for DCIS between January 2011 and June 2012. RESULTS: Of 2892 DCIS biopsies, 21% were underestimated invasive breast cancers. In multivariable analysis, risk factors were high-grade DCIS (odds ratio (OR) 1.43, 95% confidence interval (CI): 1.05-1.95), a palpable tumour (OR 2.22, 95% CI: 1.76-2.81), a BI-RADS (Breast Imaging Reporting and Data System) score 5 (OR 2.36, 95% CI: 1.80-3.09) and a suspected invasive component at biopsy (OR 3.84, 95% CI: 2.69-5.46). The predicted risk for underestimation ranged from 9.5 to 80.2%, with a median of 14.7%. Of the 596 invasive cancers, 39% had unfavourable features. CONCLUSIONS: The risk for an underestimated diagnosis of invasive breast cancer after a biopsy diagnosis of DCIS is considerable. With our prediction model, the individual risk of underestimation can be calculated based on routinely available preoperatively known risk factors ( https://www.evidencio.com/models/show/1074 ).