Abstract Background Axillary pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is achieved in a substantial part of clinically node positive breast cancer patients. Treatment of ...the axilla after NAC varies widely, and new techniques to spare patients from an axillary lymph node dissection (ALND) are being introduced. Methods This Dutch nationwide survey regarding treatment of the initially clinically node positive axilla in patients receiving NAC was conducted amongst 148 surgical oncologists during November 2014 - June 2015, to survey the diagnostic work-up, axillary mapping and willingness to omit ALND. Results Axillary ultrasound was considered a standard procedure in the diagnostic work-up by 99% of participants. The majority of 70% of participants stated that ALND could possibly be omitted in node positive patients with a favourable response to NAC. A positive correlation was observed between the total amount of patients treated, versus patients receiving NAC (P<0.01). A total of 93 respondents performed axillary response evaluation after NAC, using imaging (72%), excision of localized lymph nodes (56%) or sentinel node biopsy (SNB; 45%). Decision-making in omitting ALND was influenced by the presence of N2-3 disease, patient age and type of breast surgery. Multivariable analysis showed that clinicians who administered NAC more often, were more likely to omit ALND (P<0.01). Discussion The majority of surgeons are inclined to omit ALND in case of an axillary pCR. A large variety of techniques are being used to identify a pCR. The lack of consensus on this topic indicates the need for guidelines based on the best available evidence.
Coinciding with the relatively good and improving prognosis for patients with stage I–III breast cancer, late recurrences, new primary tumours and late side-effects of treatment may occur. We gained ...insight into prognosis for long-term breast cancer survivors.
Data on all 205 827 females aged 15–89 diagnosed with stage I–III breast cancer during 1989–2008 were derived from the Netherlands Cancer Registry. Conditional 5-year relative survival was calculated for every subsequent year from diagnosis up to 15 years.
For stage I, conditional 5-year relative survival remained ∼95% up to 15 years after diagnosis (a stable 5-year excess mortality rate of 5%). For stage II, excess mortality remained 10% for those aged 15–44 or 45–59 and 15% for those aged 60–74. For stage III, excess mortality decreased from 35% at diagnosis to 10% at 15 years for those aged 15–44 or 45–59, and from ∼40% to 30% for those aged ≥60.
Patients with stage I or II breast cancer had a (very) good long-term prognosis, albeit exhibiting a small but significant excess mortality at least up to 15 years after diagnosis. Improvements albeit from a lower level were mainly seen for patients who had been diagnosed with stage III disease. Caregivers can use this information to better inform (especially disease-free) cancer survivors about their actual prognosis.
Background
Evidence and consensus is lacking in international guidelines regarding axillary treatment recommendations for patients in whom a sentinel lymph node (SLN) cannot be visualized (non-vSLN) ...during the sentinel node procedure. In this study we aimed to determine the prevalence of non-vSLNs in a Dutch population of breast cancer patients and to examine predictors and survival rate for non-vSLN.
Methods
A nationwide, retrospective, population-based study was performed including 116,920 patients with invasive breast cancer who underwent a SLN procedure in the Netherlands between January 2005 and December 2013.
Results
Of the 76,472 clinically negative patients who underwent a SLN procedure, 1924 patients (2.5%) had a non-vSLN, of whom 1552 (80.7%) underwent an ALND. Multivariate analysis showed predictive factors for non-vSLN: older age (
p
< 0.001), diagnosis in the period 2005–2009 (
p
< 0.001), larger tumor size (
p
= 0.003), and extensive nodal involvement (
p
< 0.001). Multivariate survival analysis showed a significantly worse survival (HR 1.18, 95% CI 1.03–1.34,
p
= 0.015) for non-vSLNs patients. However, in the non-vSLN group, an ALND was not statistically significantly associated with a better survival (HR 0.96, 95% CI 0.53–1.75,
p
= 0.891).
Conclusion
Patients with non-vSLNs had less favorable disease characteristics and a worse survival compared to patients with a visualized SLN. Performing an ALND was not associated with a significantly better survival in patients with non-vSLNs. However, further research on the necessity of axillary treatment in this specific patient group is required.
Background
Axillary status in invasive breast cancer, established by sentinel lymph node biopsy (SLNB) or ultrasound-guided lymph node biopsy, is an important prognostic indicator. The ACOSOG Z0011 ...trial showed that axillary dissection may be redundant in selected sentinel node-positive patients, raising questions on the applicability of these conclusions on ultrasound positive patients. The purpose of this study was to evaluate potential differences in patient and tumor characteristics and survival between axillary node positive patients after ultrasound (US group) or sentinel lymph node procedure (SN group).
Methods
Patients diagnosed with invasive breast cancer at the Máxima Medical Center between January 2006 and December 2011 were studied.
Results
In total, 302 node-positive cases were included: 139 and 163 cases in the US and SN groups, respectively. Patients in the US group were older at diagnosis (
p
< 0.001), more often had palpable nodes (
p
< 0.001), mastectomy (
p
< 0.001), larger tumors (
p
< 0.001), higher tumor grade (
p
= 0.001), lymphovascular invasion (
p
= 0.035), a positive Her2Neu (
p
= 0.006), and a negative hormonal receptor status (
p
= 0.003). Also, they were more likely to have more lymph nodes with macrometastases (
p
< 0.001), extranodal extension (
p
< 0.001), and involvement of level-III-lymph node (
p
< 0.001). Finally, they showed a worse disease-free survival hazard ratio (HR) = 2.71; 95 % confidence interval (CI) = 1.49–4.92 and overall survival (HR = 2.67; 95 % CI = 1.48–4.84) than the SN group.
Conclusions
These results suggest that ultrasound-positive patients have less favorable disease characteristics and a worse prognosis than SN-positive patients. Therefore, we conclude that omitting an ALND is as yet only applicable, as concluded in the Z0011, in patients with a positive SLNB.
Hormone receptor (HR) status is an important prognostic factor for patients with metastatic breast cancer (MBC) and is also correlated with other prognostic factors, such as initial lymph node ...status, HER2-Neu status and age. The prognostic value of these other factors, however, is unknown when stratified by HR positive versus HR negative patients. The aim of this study was to evaluate prognostic factors for MBC survival in relation to HR status. Dutch women diagnosed with breast cancer in 2003–2006 treated with curative intent who developed MBC within 5 years of follow-up were selected from the Netherlands cancer registry (
N
= 2,001). Independent prognostic factors for survival after metastatic occurrence were determined by multivariable Cox survival analyses stratified by HR status. Interactions between HR status and prognostic factors were determined. Median survival for MBC patients with HR negative (HR−) tumours was 8 months, compared to 19 months for HR positive (HR+) patients. The prognostic value of lymph node status, HER2-Neu status, adjuvant endocrine treatment and first-line palliative chemotherapy was dependent on HR status. Initial lymph node status was independently associated with survival in HR− patients, but not in HR+ patients. HER2-Neu positive status was associated with better survival in both HR+ and HR− patients, although the association was stronger in HR− patients. Similarly, patients treated with first-line palliative chemotherapy fared better, especially HR− patients. HR+ patients had worse survival if they had received adjuvant endocrine treatment. This study shows that the prognostic value of various factors depends on HR status in MBC. This information may help physicians to determine individual prognostic profiles and therapeutic strategies for MBC patients.
•The incidence of delayed breast cancer diagnosis after screening has decreased.•Most of these diagnostic delays are longer than 24 months.•Quality assurance should focus on screening programmes and ...hospitals handling recall.
To determine the extent and characteristics of delay in breast cancer diagnosis in women recalled at screening mammography.
We included a consecutive series of 817,656 screens of women who received biennial screening mammography in a Dutch breast cancer screening region between 1997 and 2016. During at least 3.5 years follow-up, radiological reports and biopsy reports were collected of all recalled women. The inclusion period was divided into four cohorts of four years each. We determined the number of screen-detected cancers and their characteristics, and assessed the proportion of recalled women who experienced a diagnostic delay of at least 4 months in breast cancer confirmation.
The proportion of recalled women who experienced diagnostic delay decreased from 7.5 % in 1997−2001 (47/623) to 3.0 % in 2012−2016 (67/2223, P < 0.001). The proportion of women with a delay of at least two years increased from 27.7 % (13/47) in 1997−2001 to 75.7 % (53/70) in 2012−2016 (P < 0.001).
Cancers with a diagnostic delay > 2 years were more frequently invasive (P = 0.009) than cancers with a diagnostic delay of 4−24 months. The most frequent cause of diagnostic delays was incorrect radiological classifications by clinical radiologists (55.2 % overall) after recall.
The proportion of recalled women with a delayed breast cancer diagnosis has more than halved during two decades of screening mammography. Delays in breast cancer diagnosis are characterized by longer delay intervals, although the proportion of these delays among all screen-detected cancers has not increased. Preventing longer delays in breast cancer confirmation may help improve breast cancer survival.
Abstract Introduction Nowadays, axillary sentinel node (SN) biopsy is a standard procedure in the staging of breast cancer. Although the internal mammary (IM) lymph node status is a major independent ...prognostic factor in breast cancer patients, sampling of IM sentinel nodes (IMSNs) is not performed routinely. The aim of this study was to determine the likelihood of finding IM lymph node metastases in case of IM hotspots on lymphoscintigraphy and evaluate the relevance of IMSN biopsy as a method to improve staging. Patients and methods Between April 1997 and May 2006, a total of 1008 consecutive patients with clinically node-negative operable primary breast cancer were enrolled in a prospective study on SN biopsy. Both axillary and IMSNs were sampled, based on lymphoscintigraphy, intraoperative gamma probe detection and blue dye mapping, using 10 mCi (370 MBq)99m Tc-nanocolloid injected peritumorally, and 0.5–1.0 ml Patent Blue V injected intradermally. Results Lymphoscintigraphy showed axillary sentinel nodes in 98% (989/1008) and IMSNs in 20% of the patients (196/1008). Sampling the IM basin, as based on the results of lymphoscintigraphy, was successful in 71% of the patients (139/196) and revealed metastases in 22% (31/139). In 29% of the patients with positive IMSNs (9/31) no axillary metastases were found. Conclusion Evaluation of IMSNs improves nodal staging in breast cancer. Patients with IM hotspots on lymphoscintigraphy have a substantial risk (22%) of metastatic involvement of the IM chain. In addition, true IM node-negative patients can be spared the morbidity associated with adjuvant radiotherapy.
Abstract Background Axillary reverse mapping (ARM) is a technique to map and preserve upper extremity lymphatic drainage during axillary lymph node dissection (ALND) in breast cancer patients. We ...prospectively evaluated the metastatic involvement of ARM-nodes in patients who underwent an ALND for clinically node positive disease following (neo)adjuvant chemotherapy (NAC) in comparison to patients in whom primary ALND was performed without NAC. Patients and methods Patients with clinically node positive invasive breast cancer, confirmed by fine needle aspiration cytology and scheduled for primary ALND were enrolled in the study. Patients were separated into two groups: one group treated with NAC (NAC+ group) and one group not treated with NAC (NAC− group). ARM was performed in all patients by injecting blue dye into the ipsilateral upper extremity. During ALND, ARM-nodes were first identified and removed separately, followed by a standard ALND. Results 91 patients were included in the NAC+ and 21 patients in the NAC− group. There was no difference in the ARM visualization rate between the two groups (86.8% for NAC+ group versus 90.5% for NAC− group, P = 0.647). In the NAC+ group 16.5% of the patients had metastatic involvement of the ARM-nodes versus 36.8% of the patients in the NAC− group ( P = 0.048). Conclusion The risk of metastatic involvement of ARM-nodes in clinically node positive breast cancer patients is significantly lower in patients who have received NAC.
Three species of giant barrel sponge are currently recognized in two distinct geographic regions, the tropical Atlantic and the Indo-Pacific. In this study, we used molecular techniques to study ...populations of giant barrel sponges across the globe and assessed whether the genetic structure of these populations agreed with current taxonomic consensus or, in contrast, whether there was evidence of cryptic species. Using molecular data, we assessed whether giant barrel sponges in each oceanic realm represented separate monophyletic lineages. Giant barrel sponges from 17 coral reef systems across the globe were sequenced for mitochondrial (partial CO1 and ATP6 genes) and nuclear (ATPsβ intron) DNA markers. In total, we obtained 395 combined sequences of the mitochondrial CO1 and ATP6 markers, which resulted in 17 different haplotypes. We compared a phylogenetic tree constructed from 285 alleles of the nuclear intron ATPsβ to the 17 mitochondrial haplotypes. Congruent patterns between mitochondrial and nuclear gene trees of giant barrel sponges provided evidence for the existence of multiple reproductively isolated species, particularly where they occurred in sympatry. The species complexes in the tropical Atlantic and the Indo-Pacific, however, do not form separate monophyletic lineages. This rules out the scenario that one species of giant barrel sponge developed into separate species complexes following geographic separation and instead suggests that multiple species of giant barrel sponges already existed prior to the physical separation of the Indo-Pacific and tropical Atlantic.
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