OBJECTIVE:The MARI procedure marking the axillary lymph node with radioactive iodine (I) seeds is a new minimal invasive method to assess the pathological response of nodal metastases after ...neoadjuvant systemic treatment (NST) in patients with breast cancer. This method allows axilla-conserving surgery in patients responding well to NST.
METHODS:Prior to NST, proven tumor-positive axillary lymph nodes were marked with a I seed. This marked lymph node is the so-called MARI-node. After NST, the MARI node was selectively removed using a γ-detection probe. A complementary axillary lymph node dissection was performed in all patients to assess whether pathological response in the MARI node was indicative for the pathological response in the additional lymph nodes.
RESULTS:A tumor-positive axillary lymph node was marked with a I seed in 100 patients. The MARI node was successfully identified in 97 of these 100 patients (identification rate 97%). Two patients did not undergo subsequent axillary lymph node dissection, leaving 95 patients for further analysis. The MARI node contained residual tumor cells in 65 of these 95 patients. In the other 30 patients, the MARI node was free of tumor, but additional positive lymph nodes were found in 5 patients. Thus, the MARI procedure correctly identified 65 of 70 patients with residual axillary tumor activity (false negative rate 5/70 = 7%).
CONCLUSIONS:This study shows that marking and selectively removing metastatic lymph nodes after neoadjuvant systemic treatment has a high identification rate and a low false negative rate. The tumor response in the marked lymph node may be used to tailor further axillary treatment after NST.
Patients with 70-gene signature ultralow-risk breast cancers have shown excellent survival in historic cohorts, including randomized trials. The ultralow-risk subgroup was characterized to help avoid ...overtreatment. We evaluated outcomes of ultralow-risk patients in the largest cohort to date.
Of the 6,693 patients enrolled in the EORTC-10041/BIG-3-04 randomized phase III MINDACT trial, profiling revealed an ultralow-risk 70-gene signature in 1,000 patients (15%). Distant metastasis-free interval (DMFI) and breast cancer-specific survival (BCSS) were assessed in patients stratified by 70-gene signature result (high, low, and ultralow) by Kaplan-Meier analysis and hazard ratios with 95% CI from Cox regression.
Median follow-up was 8.7 years. Of the ultralow-risk patients (n = 1,000), 67% were > 50 years, 81% had tumors ≤ 2 cm, 80% were lymph node-negative, 96% had grade 1 or 2 tumors, and 99% were estrogen receptor (ER)-positive. Systemic therapy was received by 84% of patients (69% endocrine therapy, 14% endocrine therapy plus chemotherapy, 1% other) and 16% received no adjuvant systemic treatment. The 8-year DMFI for ultralow-risk patients was 97.0% (95% CI, 95.8 to 98.1), which was 2.5% higher than for patients with low-risk tumors (n = 3,295, 94.5% 95% CI, 93.6 to 95.3). The hazard ratio for DMFI was 0.65 (95% CI, 0.45 to 0.94) for ultralow versus low risk, after adjusting for clinical-pathologic and treatment characteristics. The 8-year BCSS for ultralow-risk patients was 99.6% (95% CI, 99.1 to 100).
Patients with an ultralow-risk 70-gene signature have the best prognosis, distinctive from low risk, with 8-year BCSS above 99%, and very few patients developed distant metastases with an 8-year DMFI rate of 97%. These patients could be candidates for further de-escalation of treatment, to avoid overtreatment and the risk of side effects.
This study aims to evaluate the response to and surgical benefits of neoadjuvant endocrine therapy (NET) in ER+/HER2-breast cancer patients who are clinically high risk, but genomic low risk ...according to the 70-gene signature (MammaPrint).
Patients with ER+/HER2-invasive breast cancer with a clinical high risk according to MINDACT, who had a genomic low risk according to the 70-gene signature and were treated with NET between 2015 and 2023 in our center, were retrospectively analyzed. RECIST 1.1 criteria were used to assess radiological response using MRI or ultrasound. Surgical specimens were evaluated to assess pathological response. Two breast cancer surgeons independently scored the eligibility of breast conserving therapy (BCS) pre- and post- NET.
Of 72 included patients, 23 were premenopausal (100% started with tamoxifen of which 4 also received OFS) and 49 were postmenopausal (98% started with an aromatase inhibitor). Overall, 8 (11%) showed radiological complete response. Only 1 (1.4%) patient had a pathological complete response (RCB-0) and 68 (94.4%) had a pathological partial response (RCB-1 or RCB-2). Among the 26 patients initially considered for mastectomy, 14 (53.8%) underwent successful BCS. In all 20 clinical node-positive patients, a marked axillary lymph node was removed to assess response. Four out of 20 (20%) patients had a pathological complete response of the axilla.
The study showed that a subgroup of patients with a clinical high risk and a genomic low risk ER+/HER2-breast cancer benefits from NET resulting in BCS instead of a mastectomy. Additionally, NET may enable de-escalation in axillary treatment.
•Population: ER+/HER2-breast cancer treated with neoadjuvant endocrine therapy.•Inclusion criteria: clinical high risk & low-risk 70-gene signature.•Conversion to breast-conserving surgery in 53.8%.
Tailored recommendation for adjuvant chemotherapy in breast cancer patients is of great importance. This survey assessed agreement among oncologists on risk assessment and chemotherapy ...recommendation, the impact of adding the 70-gene signature to clinical-pathological characteristics, and changes over time.
A survey consisting of 37 discordant patient cases from the MINDACT trial (T1-3N0-1M0) was sent to European breast cancer specialists for assessment of risk (high or low) and chemotherapy administration (yes or no). In 2015 the survey was sent twice (survey 1 and 2), several weeks apart, and in 2021 a third time (survey 3). Only the second and third surveys included the 70-gene signature result.
41 breast cancer specialists participated in all three surveys. Overall agreement between respondents decreased slightly between survey 1 and 2, but increased again in survey 3. Over time there was an increase in agreement with the 70-gene signature result on risk assessment, 23% in survey 2 versus 1 and 11% in survey 3 versus 2. With information available indicating a low risk 70-gene signature (n = 25 cases), 20% of risk assessments changed from high to low and 19% of recommendations changed from yes to no chemotherapy in survey 2 versus 1, further increasing with 18% and 21%, respectively, in survey 3 versus 2.
There is a variability in risk assessment of early breast cancer patients among breast cancer specialists. The 70-gene signature provided valuable information, resulting in fewer patients being assessed as high risk and fewer recommendations for chemotherapy, increasing over time.
•Risk assessment of early breast cancer patients varies among breast specialists.•The 70-gene signature provides valuable information for risk assessment.•Information on the 70-gene signature resulted in fewer high risk assessments.•Information on the 70-gene signature resulted in fewer chemotherapy recommendations.•Agreement with the 70-gene signature result increased over time.
The aim of our study is to analyze patterns in treatment and outcome in a population-based series of patients with borderline and malignant phyllodes tumors (PT).
Data on all patients with a ...borderline or malignant PT (1989–2020) were extracted from the Netherlands Cancer Registry and the Dutch nationwide pathology databank (Palga) and retrospectively analyzed.
We included 921 patients (borderline PT n = 452 and malignant PT n = 469). Borderline PT patients more often had breast-conserving surgery (BCS) as final surgery (81 vs. 46%). BCS rates for borderline PT increased over time (OR 1.08 per year, 95%CI 1.04 - 1.13, P < 0.001). In malignant PT adjuvant radiotherapy was given in 14.7%; this rate increased over time (OR 1.07 per year, 95%CI 1.02 – 1.13, P = 0.012). Local recurrence rate (5-year estimate of cumulative incidence) was 8.7% (95%CI 6.0–11.4) for borderline PT and 11.7% (95%CI 8.6–14.8) for malignant PT (P = 0.187) and was related to tumor size ≥ 20 mm (HR 10.6 (95%CI 1.5–76.8) and positive margin (HR 3.0 (95%CI 1.6–5.6), p < 0.001), but not to negative margin width (HR 1.3 ( 95%CI 0.7–2.3), p = 0.350)). Distant metastasis occurred only in malignant PT with a 5-year cumulative incidence of 4.7% (95%CI 3.3 – 6.1).
This population-based series showed an increase in BCS in borderline PT and an increase in adjuvant radiotherapy in malignant PT over time. We identified malignant PT, BCS, larger tumor size and positive final margins as possible risk factors for local recurrence. Small but negative margins can be accepted.
•Increased breast conserving surgery rates over time for borderline phyllodes tumors.•Increased radiotherapy rates over time for malignant PT.•Malignant phyllodes tumor and tumor size ≥ 20 mm elevate local recurrence risk.•Surgical risk factors: Breast-conserving surgery and final positive margins.•Small but negative margins can be accepted.
Background
Phyllodes tumors (PTs) are rare tumors of the breast. The current National Comprehensive Cancer Network (NCCN) guidelines recommend excision of benign PTs, accepting close or positive ...margins. Controversy about the optimal treatment for benign PTs remains, especially regarding the preferred margin width after surgical excision and the need for follow-up evaluation.
Methods
A nationwide retrospective study analyzed the Dutch population from 1989 to 2022. All patients with a diagnosis of benign PT were identified through a search in the Dutch nationwide pathology databank (Palga). Information on age, year of diagnosis, size of the primary tumor, surgical treatment, surgical margin status, and local recurrence was collected.
Results
The study enrolled 1908 patients with benign PT. The median age at diagnosis was 43 years (interquartile range IQR, 34–52 years), and the median tumor size was 30 mm (IQR, 19–40 mm). Most of the patients (95%) were treated with breast-conserving surgery (BCS). The overall local recurrence rate was 6.2%, and the median time to local recurrence was 31 months (IQR, 15–61 months). Local recurrence was associated with bilaterality of the tumor (odds ratio OR, 4.91; 95% confidence interval CI, 2.95–28.30) and positive margin status (OR, 2.51; 95% CI 1.36–4.63). The local recurrence rate was 8.9% for the patients with positive excision margins and 4.0% for the patients with negative excision margins. Notably, for 27 patients (22.6%) who experienced a local recurrence, histologic upgrading of the recurrent tumor was reported, 7 (5.9%) of whom had recurrence as malignant lesions.
Conclusions
This nationwide series of 1908 patients showed a low local recurrence rate of 6.2% for benign PT, with higher recurrence rates following positive margins.
Prognostic gene expression signatures can be used in combination with classical clinicopathological factors to guide adjuvant chemotherapy decisions in ER-positive, HER2-negative breast cancer. ...However, long-term outcome data after introduction of genomic testing in the treatment decision-making process are limited.
In the prospective RASTER study, the tumours of 427 patients with cTanyN0M0 breast cancer were tested to assess the 70-gene signature (MammaPrint). The results were provided to their treating physician to be incorporated in the decision-making on adjuvant systemic therapy. Here, we report the long-term outcome of the 310 patients with ER-positive, HER2-negative tumours by clinical and genomic risk categories at a median follow-up of 10.3 years.
Among the clinically high-risk patients, 45 (49%) were classified as genomically low risk. In this subgroup, at 10 years, distant recurrence free interval (DRFI) was similar between patients treated with (95.7% 95% CI 87.7–100) and without (95.5% 95% CI 87.1–100) chemotherapy. Within the group of clinically low-risk patients, 56 (26%) were classified as genomically high risk. Within the clinically low-risk group, beyond 5 years, a difference emerged between the genomically high- and low-risk subgroup resulting in a 10-year DRFI of 84.3% (95% CI 74.8–95.0) and 93.4% (95% CI 89.5–97.5), respectively. Interestingly, genomic ultralow-risk patients have a 10-year DRFI of 96.7% (95% CI 90.5–100), largely (79%) without systemic therapy.
These data confirm that clinically high-risk, genomically low-risk tumours have an excellent outcome in the real-world setting of shared decision-making. Together with the updated results of the MINDACT trial, these data support the use of the MammaPrint, in ER-positive, HER2-negative, node-negative, clinically high-risk breast cancer patients.
ISRCTN71917916
•Clinical high-risk, genomic low-risk tumours have similar DRFI with or without chemo.•Genomic ultralow-risk tumours have a good outcome largely without systemic therapy.•10-year DRFI in clinical low-risk, genomic high-risk tumours suggest undertreatment.
Pediatric thyroid carcinoma is a rare malignancy and data on long-term oncological outcomes are sparse. The aim of this study was to describe the long-term oncological outcomes of pediatric papillary ...thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) in a national cohort, and to identify risk factors for recurrence.
We conducted a nationwide, retrospective cohort study, in which we combined two national databases. Patients aged <18 years, diagnosed with PTC or FTC in the Netherlands between 2000 and 2016, were included. pT-stage, pN-stage, multifocality and angioinvasion were included in a Cox-regression analysis for the identification of risk factors for recurrence.
133 patients were included: 110 with PTC and 23 with FTC. Patients with PTC most often presented with pT2 tumors (24%) and pN1b (45%). During a median follow-up of 11.3 years, 21 patients with PTC developed a recurrence (19%). Nineteen recurrences were regional (91%) and 2 were pulmonary (9%). No risk factors for recurrence could be determined. One patient who developed pulmonary recurrence died two years later. Cause of death was not captured. Patients with FTC most often presented with pT2 tumors (57%). One patient presented with pN1b (4%). In 70%, no lymph nodes were collected. None of the patients with FTC developed a recurrence or died.
Pediatric PTC and FTC are two distinct diseases. Recurrence in pediatric PTC is common, but in FTC it is not. Survival for both pediatric PTC and FTC is very good.
A breast cancer gene signature for indolent disease Delahaye, Leonie J. M. J.; Drukker, Caroline A.; Dreezen, Christa ...
Breast cancer research and treatment,
07/2017, Letnik:
164, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Purpose
Early-stage hormone-receptor positive breast cancer is treated with endocrine therapy and the recommended duration of these treatments has increased over time. While endocrine therapy is ...considered less of a burden to patients compared to chemotherapy, long-term adherence may be low due to potential adverse side effects as well as compliance fatigue. It is of high clinical utility to identify subgroups of breast cancer patients who may have excellent long-term survival without or with limited duration of endocrine therapy to aid in personalizing endocrine treatment.
Methods
We describe a new ultralow risk threshold for the 70-gene signature (MammaPrint) that identifies a group of breast cancer patients with excellent 20 year, long-term survival prognosis. Tumors of these patients are referred to as “indolent breast cancer.” We used patient series on which we previously established and assessed the 70-gene signature high–low risk threshold.
Results
In an independent validation cohort, we show that patients with indolent breast cancer had 100% breast cancer-specific survival at 15 years of follow-up.
Conclusions
Our data indicate that patients with indolent disease may be candidates for limited treatment with adjuvant endocrine therapy based on their very low risk of distant recurrences or death of breast cancer.
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