Reliability of receptor assessment on core needle biopsy in breast cancer patients

We compared the breast core needle biopsy and the resection specimen with respect to estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2) status to identify predictors for discordant findings. We retrospectively collected data from 526 newly diagnosed breast cancer patients. ER, PR and HER2 status had been assessed in both the core needle biopsy and resection specimen. The assessment of ER by immunohistochemistry (IHC) in core needle biopsy was false negative in 26.5% and false positive in 6.8% of patients. For the PR status the false negative and false positive results of core needle biopsy were 29.6% and 10.3%, respectively. The results of the HER2 status, as determined by IHC and silver in situ hybridization (SISH), were false negative in 5.4% and false positive in 50.0%. We need to be aware of the problem of false negative and false positive test results in ER, PR and HER2 assessment in core needle biopsy and the potential impact on adjuvant systemic treatment. With current techniques, we recommend using the resection specimen to measure these receptors in patients without neoadjuvant treatment. A better alternative might be the use of tissue microarray, combining both core needle biopsy and resection specimen.     

Models predicting non-sentinel node involvement also predict for regional recurrence in breast cancer patients without axillary treatment

Background

Non-SN prediction models are frequently used in clinical decision making to identify patients that may not need axillary treatment, but these models still need to be validated by follow-up data. Our purpose was the validation of non-sentinel node (SN) prediction models in predicting regional recurrences in patients without axillary treatment.

Methods

We followed a cohort of 486 women with favorable primary tumor characteristics and pN0(i+)(sn) or pN1mi(sn) for median 4.5 years. None of the patients underwent axillary treatment. Based on four published non-SN prediction models, the threshold allowing separation into low versus high-risk on non-SN involvement was set at 10%.

Results

Overall 5-year regional recurrence rate was 3.0% (SE, ±0.1%). Using the Tenon scoring system, 438 low-risk patients had a 5-year regional recurrence rate of 2.3% (±0.8%), and 48 high-risk patients a recurrence rate of 10.1% (±0.4%). The MSKCC nomogram identified 300 low-risk patients with a recurrence rate of 2.8% (±1.1%), versus 166 high-risk patients with a rate of 3.4% (±0.5%) (20 patients not assessable). The Stanford nomogram identified 21 high-risk patients without recurrence, and 465 low-risk patients with a 3.2% (±0.9%) recurrence rate. A Dutch model discriminated between 384 low-risk patients with a recurrence rate of 2.2% (±0.8%) and 102 high-risk patients with a rate of 6.3% (±2.9%).

Conclusion

The Tenon scoring system outperformed the other models as it identified the largest subgroup of patients with low recurrence rate. In patients resembling our cohort we would recommend axillary treatment if they had a Tenon score above 3.5.     

The implementation of CDK 4/6 inhibitors and its impact on treatment choices in HR+/HER2− advanced breast cancer patients: A study of the Dutch SONABRE Registry

In August 2017, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have been reimbursed in the Netherlands for patients with hormone receptor positive (HR+), HER2 negative (HER2?) advanced breast cancer (ABC). This study evaluates the implementation of CDK4/6 inhibitors and changes in treatment choices in the Netherlands. All patients diagnosed with HR+/HER2? ABC in 2009 to 2018 in seven hospitals were selected from the Southeast Netherlands Advanced Breast cancer (SONABRE) registry. The 2-year cumulative use of CDK4/6 inhibitors since reimbursement date (August 2017) was assessed using competing-risk methodology in two cohorts. The first cohort included patients with ABC diagnosis between August 2017 and December 2018. The second cohort included patients with ABC diagnosis between 2009 and August 2017, and still alive on August 1, 2017. In addition, treatment choices in the first three lines of therapy in calendar years 2009 to 2018 were evaluated for the total study population. Among patients diagnosed since August 2017 (n = 214), 50% (95% confidence interval [CI] = 43-57) received CDK4/6 inhibitors within 2 years beyond diagnosis. Of eligible patients diagnosed before August 2017 (n = 417), 31% (95% CI = 27-36) received CDK4/6 inhibitors within 2 years following reimbursement. Another 20% of both cohorts are still CDK4/6 inhibitor naïve and on first-line therapy. The use of chemotherapy decreased in first two lines of therapy between 2009 and 2018 (first-line: 29%-13%; second-line: 26%-19%). The implementation rate of CDK4/6 inhibitors since reimbursement is currently 50% within 2 years beyond diagnosis and is expected to increase further. The implementation of targeted therapy decreased the use of chemotherapy as first-line therapy.     

Implementation of trastuzumab in conjunction with adjuvant chemotherapy in the treatment of non-metastatic breast cancer in the Netherlands

Trastuzumab in conjunction with adjuvant chemotherapy markedly improves outcome. In the Netherlands, a national guideline was released in September 2005 stating that trastuzumab should be given in conjunction with adjuvant chemotherapy in women with HER2-positive breast cancer. Aim of this study was to identify the number of women with HER2-positive breast cancer and to evaluate the level of implementation of adjuvant trastuzumab in clinical practice nationwide. Women diagnosed with primary breast cancer between September 2005 and January 2007 were selected from the Netherlands Cancer Registry (NCR). HER2 status, adjuvant treatment and reasons to withhold trastuzumab were registered. 14,934 Breast cancer patients were diagnosed in this period of whom 1,928 (13%) had a HER2-positive tumour. Of all HER2-positive women receiving adjuvant chemotherapy, 66 (6%) did not receive trastuzumab. This percentage decreased from 10% at the time of introduction of the guideline to 4% in the study period September 2005–December 2006. Most common reasons to withhold trastuzumab were cardiovascular disease (29%) and patient refusal (21%). Of all HER2-positive patients who received adjuvant chemotherapy, 94% received trastuzumab. The implementation of trastuzumab in clinical practice was realized within 8 months after introduction of the new guideline.     

Epirubicin and paclitaxel with G-CSF support in first line metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated chemotherapy

An increased dose-intensity can be achieved by either higher dose of chemotherapy per cycle (dose-escalation) or by shortening the interval between cycles (dose-dense). This multicenter randomized phase II study assessed the efficacy and safety of two different approaches: epirubicin 110 mg/m(2) combined with paclitaxel 200 mg/m(2) every 21 days and epirubicin 75 mg/m(2) combined with paclitaxel 175 mg/m(2) every 10 days, both supported with G-CSF. Patients with advanced breast cancer and without prior palliative chemotherapy were scheduled for 6 cycles. Evaluable for response were 101 patients and for toxicity 106 patients. Grade ≥ 3 toxicities occurred in 39% of patients in the dose-escalated arm and in 29% of the dose-dense arm, mainly febrile neutropenia, thrombocytopenia, neurotoxicity and (asymptomatic) cardiotoxicity. The median delivered cumulative doses for epirubicin/paclitaxel were 656/1194 and 448/1045 mg/m(2), treatment durations were 126 and 61 days, and delivered dose intensities were 36/67 and 51/120 mg/m(2)/week for the dose-escalated and dose-dense arm, respectively. Response rates were 75 and 70%, the progression-free survival 6 and 7 months, respectively. Dose-dense chemotherapy with a lower cumulative dose, a halved treatment time, but a higher dose-intensity may be as effective and safe as dose-escalated chemotherapy. The value of dose-densification over standard scheduled chemotherapy regimes yet needs to be determined.     

Quality of integrated care for patients with nonsmall cell lung cancer: variations and determinants of care

BACKGROUND: In the current study, the authors focused on determinants influencing the quality of care and variations in the actual quality of integrated care for patients with nonsmall cell lung cancer (NSCLC) to estimate whether there is room for improvement. METHODS: The authors tested the quality of integrated care for 276 NSCLC patients with 14 quality indicators of professional (4 indicators), organizational (3 indicators), and patient-oriented quality (7 indicators). Patient characteristics and actual care data were derived from medical record data, patient-oriented care was derived from patient questionnaires, and professional and hospital characteristics were derived from questionnaires for professionals. The performance measure was the proportion of patients to whom the indicator applied who had positive scores on the indicator. Multilevel logistic regression analysis determined the influence of patient, professional, and hospital characteristics on care. RESULTS: With regard to professional quality, the proportions of patients who underwent fluorodeoxyglucose-positron emission tomography or cervical mediastinoscopy according to the guideline criteria were 88% and 84%, respectively. Only 50% of the biopsies were adequately obtained during mediastinoscopy, and in 3% of the patients with clinical stage III disease (based on the TNM classification) there was a search for brain metastases before the initiation of combination therapy. With regard to organizational quality, the diagnostic route of 79% of the patients was completed within 21 days; 51% of patients began therapy within 35 days and 57% were discussed during multidisciplinary consultation. All but 1 patient-oriented quality indicator scored /=20% with regard to 11 of the 14 indicators. The patient-related determinants "stage of disease," "age," and "comorbidity" were found to influence the indicator scores the most. CONCLUSIONS: The quality of integrated care (especially patient-oriented care) for NSCLC patients needs improvement. Patient characteristics appear to influence performance more than professional or hospital characteristics.     

Histological type is not an independent prognostic factor for the risk pattern of breast cancer recurrences

Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC) and appears to have a distinct biology. Inconsistent findings regarding disease-free survival (DFS) are probably due to the fact that histologic type is related to hormone receptor status. This study aims to determine whether the type of the primary breast cancer histology is an independent prognostic factor for DFS, the risk pattern of loco-regional recurrences and distant metastases (DM), and whether it is a prognostic factor for the site of DM. All Dutch women diagnosed between 2003 and 2005 with ILC (n = 2,949) or IDC (n = 22,378) were selected from the Netherlands Cancer Registry. DFS was assessed using proportional hazard regression analysis. Compared to patients with IDC, those with ILC were significantly older and more likely to have more than three positive lymph nodes and have larger, better differentiated, more multifocal, and hormone receptor positive tumors (all P < 0.001). ILC was more likely to metastasize to the gastrointestinal organs and bones and less likely to the lung, central nervous system, and lymph nodes. Within the ER+PR+ and ER+PR? subgroups ILC was still more likely to metastasize to gastrointestinal organs and less likely to the lung. The timing of recurrence was correlated to hormone receptor status, independent of histological type. Highest risks were observed among ER?PR? patients within 2 years of surgery. Multivariable analysis showed that histological type is not an independent significant prognostic factor of DFS for the first 3 years post-surgery and thereafter (<3 years HR 0.91, 95 % CI 0.78–1.06, >3 years HR 1.07, 95 % CI 0.88–1.30). Histological type should not be considered an important prognostic factor for the risk and risk pattern of recurrences.     

Cost-effectiveness of adjuvant systemic therapy in low-risk breast cancer patients with nodal isolated tumor cells or micrometastases

BackgroundThe cost-effectiveness of adjuvant systemic therapy in patients with low-risk breast cancer and nodal isolated tumor cells or micrometastases is unknown.Patients and methodsA cost-effectiveness analysis of adjuvant systemic therapy was carried out using the costs per 1% event prevented after 5 years of follow-up as incremental cost-effectiveness ratio (ICER). Secondary objective was to establish when adjuvant systemic therapy becomes cost saving. Patients included in the MIRROR study with isolated tumor cells or micrometastases who had a complete 5-year follow-up and who either did or did not receive systemic therapy were eligible. Sensitivity analyses were carried out.ResultsIn the no adjuvant therapy cohort (N = 366), 24.9% of patients had an event within 5 years versus 16.8% of patients in the adjuvant therapy cohort (N = 483) (P < 0.01). The ICER was €363 per 1% event prevented. Beyond 18 years after diagnosis, the extrapolated mean cumulative costs per patient in the no adjuvant therapy cohort exceeded those of the adjuvant therapy cohort.ConclusionsIn this population of breast cancer patients with isolated tumor cells or micrometastases, €36 300 had to be invested to prevent one event in 5 years of follow-up. Adjuvant systemic therapy was cost saving beyond 18 years after diagnosis.     

Hormone Treatment without Surgery for Patients Aged 75 Years or Older with Operable Breast Cancer

Purpose  

To evaluate the trend in the use of primary endocrine treatment (PET) for elderly patients with operable breast cancer and to study mean time to response (TTR), local control, time to progression (TTP), and overall survival.