Adjuvant radiotherapy (RT) after a local excision (LE) for ductal carcinoma in situ (DCIS) aims at reduction of the incidence of a local recurrence (LR). We analyzed the long-term risk on developing ...LR and its impact on survival after local treatment for DCIS.
Between 1986 and 1996, 1,010 women with complete LE of DCIS less than 5 cm were randomly assigned to no further treatment (LE group, n = 503) or RT (LE+RT group, n = 507). The median follow-up time was 15.8 years.
Radiotherapy reduced the risk of any LR by 48% (hazard ratio HR, 0.52; 95% CI, 0.40 to 0.68; P < .001). The 15-year LR-free rate was 69% in the LE group, which was increased to 82% in the LE+RT group. The 15-year invasive LR-free rate was 84% in the LE group and 90% in the LE+RT group (HR, 0.61; 95% CI, 0.42 to 0.87). The differences in LR in both arms did not lead to differences in breast cancer-specific survival (BCSS; HR, 1.07; 95% CI, 0.60 to 1.91) or overall survival (OS; HR, 1.02; 95% CI, 0.71 to 1.44). Patients with invasive LR had a significantly worse BCSS (HR, 17.66; 95% CI, 8.86 to 35.18) and OS (HR, 5.17; 95% CI, 3.09 to 8.66) compared with those who did not experience recurrence. A lower overall salvage mastectomy rate after LR was observed in the LE+RT group than in the LE group (13% v 19%, respectively).
At 15 years, almost one in three nonirradiated women developed an LR after LE for DCIS. RT reduced this risk by a factor of 2. Although women who developed an invasive recurrence had worse survival, the long-term prognosis was good and independent of the given treatment.
Few data have been reported regarding endocrine therapy (ET) in patients with small pT1a-b ER-postive breast cancer (BC). Thus, we conducted a study to detect possible survival improvements due to ET ...in such patients.
Our retrospective observational study included 5545 patients with pT1a-b ER-positive BC treated in 15 French centres, excluding patients with HER2-positive status, neoadjuvant chemotherapy, ER-negative status, unknown pN status or in situ BC. We estimated disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) via univariate analysis and multivariate Cox regression.
Most patients (80.3%: 4453) received ET and–when compared to those without ET–experienced increases of 2.5% and 3.3% in DFS and 1.9% and 4.3% in RFS after 5 and 7 years of follow-up, respectively, with little difference in OS. In Cox regression analysis, no ET was significantly associated with decreased DFS (hazard ratio, HR = 1.275, p = 0.047, 95% CI1.003–1.620) but not OS or RFS in all patients, while in 2363 patients with pT1a-b ER-positive grade 2-3 BC, no ET was significantly associated with decreased DFS (HR = 1.502, p = 0.049, 95% CI1.001–2.252), but not OS (HR = 1.361, p = 0.272). ET omission was not significantly associated with decreased survival in 3047 patients with pT1a-b ER-positive grade 1 BC.
Our results indicate that while ET provided a beneficial impact on survival to patients with pT1a-bN0 ER-positive BC—and especially in those with grade 2–3 tumours—no such impact was observed in grade 1 tumours. Consequently, ET should be discussed with these patients, particularly in those with pT1a grade 1 tumours.
•No endocrine therapy (ET) was significantly associated with decreased disease-free survival in all patients (hazard ratio = 1.275).•No ET was significantly associated with decreased disease-free survival in grade 2–3 tumours (hazard ratio = 1.502).•ET omission was not associated with decreased survival in 3047 grade 1 tumours.•ET omission may be considered in some patients with subcentimetric oestrogen receptor-positive cancer.
PTEN plays a well‐established role in the negative regulation of the PI3K pathway, which is frequently activated in several cancer types, including breast cancer. A nuclear function in the ...maintenance of chromosomal stability has been proposed for PTEN but is yet to be clearly defined. In order to improve understanding of the role of PTEN in mammary tumorigenesis in terms of a possible gene dosage effect, its PI3K pathway function and its association with p53, we undertook comprehensive analysis of PTEN status in 135 sporadic invasive ductal carcinomas. Four PTEN status groups were defined; complete loss (19/135, 14%), reduced copy number (19/135, 14%), normal (86/135, 64%) and complex (11/135, 8%). Whereas the PTEN complete loss status was significantly associated with estrogen receptor (ER) negativity (p=0.006) and in particular the basal‐like phenotype (p<0.0001), a reduced PTEN copy number was not associated with hormone receptor status or a particular breast cancer subtype. Overall, PI3K pathway alteration was suggested to be involved in 59% (79/134) of tumors as assessed by human epidermal growth factor receptor 2 overexpression, PIK3CA mutation or a complete loss of PTEN. A complex PTEN status was identified in a tumor subgroup which displayed a specific, complex DNA profile at the PTEN locus with a strikingly similar highly rearranged pan‐genomic profile. All of these tumors had relapsed and were associated with a poorer prognosis in the context of node negative disease (p=1.4 × 10−13) thus may represent a tumor subgroup with a common molecular alteration which could be targeted to improve clinical outcome.
What's new?
PTEN plays a well‐established role in the negative regulation of the PI3K pathway, which is frequently activated in breast cancer, and may also help maintain chromosomal stability. Here the authors analyzed PTEN status to improve understanding of the role of PTEN regarding a possible gene dosage effect, its PI3K pathway function, and its association with p53. Breast carcinomas were classified into 4 PTEN status groups, one of which displayed a specific, complex DNA profile and corresponded to tumors that had relapsed and presented a poorer prognosis. Furthermore, for most tumors, loss of p53 was not required to escape PTEN‐induced senescence.
A strong correlation between breast cancer (BC) molecular subtypes and axillary status has been shown. It would be useful to predict the probability of lymph node (LN) positivity.
To develop the ...performance of multivariable models to predict LN metastases, including nomograms derived from logistic regression with clinical, pathologic variables provided by tumor surgical results or only by biopsy.
A retrospective cohort was randomly divided into two separate patient sets: a training set and a validation set. In the training set, we used multivariable logistic regression techniques to build different predictive nomograms for the risk of developing LN metastases. The discrimination ability and calibration accuracy of the resulting nomograms were evaluated on the training and validation set.
Consecutive sample of 12,572 early BC patients with sentinel node biopsies and no neoadjuvant therapy. In our predictive macro metastases LN model, the areas under curve (AUC) values were 0.780 and 0.717 respectively for pathologic and pre-operative model, with a good calibration, and results with validation data set were similar: AUC respectively of 0.796 and 0.725. Among the list of candidate's regression variables, on the training set we identified age, tumor size, LVI, and molecular subtype as statistically significant factors for predicting the risk of LN metastases.
Several nomograms were reported to predict risk of SLN involvement and NSN involvement. We propose a new calculation model to assess this risk of positive LN with similar performance which could be useful to choose management strategies, to avoid axillary LN staging or to propose ALND for patients with high level probability of major axillary LN involvement but also to propose immediate breast reconstruction when post mastectomy radiotherapy is not required for patients without LN macro metastasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
To present our single-centre prospective experience on the use of cryoablation (CA) applied to treat primary breast cancer (BC) in a cohort of patients unsuitable for surgical treatment.
...Materials and Methods
Twenty-three consecutive post-menopausal female patients (median age 85 years; range 56–96) underwent percutaneous CA of unifocal, biopsy-proven BC, under ultrasound/computed tomography (US/CT) guidance. Clinical and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) follow-ups were systematically scheduled at 3, 12, 18 and 24 months. Local tumour control was assessed by comparing baseline and follow-up DCE-MRI.
Results
Twenty-three BC (median size 14 mm) were treated under local anaesthesia (78.3 %) or local anaesthesia and conscious sedation (21.7 %). Median number of cryo-probes applied per session was 2.0. A “dual-freezing” protocol was applied for the first ten patients and a more aggressive “triple-freezing” protocol for the remaining 13. Median follow-up was 14.6 months. Five patients recurred during follow-up and two were successfully re-treated with CA. Five patients presented immediate CA-related complications: four hematomas evolved uneventfully at 3-month follow-up and one skin burn resulted in skin inflammation and skin retraction at 3 and 12 months, respectively.
Conclusions
Percutaneous CA is safe and well tolerated for non-resected elderly BC patients. Procedures can be proposed under local anaesthesia only. Given the insulation properties of the breast gland, aggressive CA protocols are required. Prospective studies are needed to better understand the potential role of CA in the local treatment of early BC.
Three randomized trials have concluded at non inferiority of omission of complementary axillary lymph node dissection (cALND) for patients with involved sentinel node (SN). However, we can outline ...strong limitations of these trials to validate this attitude with a high scientific level. We designed the SERC randomized trial ( ClinicalTrials.gov , number NCT01717131) to compare outcomes in patients with SN involvement treated with ALND or no further axillary treatment. The aim of this study was to analyze results of the first 1000 patients included.
SERC trial is a multicenter non-inferiority phase 3 trial. Multivariate logistic regression analysis was used to identify independent factors associated with adjuvant chemotherapy administration and non-sentinel node (NSN) involvement.
Of the 963 patients included in the analysis set, 478 were randomized to receive cALND and 485 SLNB alone. All patient demographics and tumor characteristics were balanced between the two arms. SN ITC was present in 6.3% patients (57/903), micro metastases in 33.0% (298), macro metastases in 60.7% (548) and 289 (34.2%) were non eligible to Z0011 trial criteria. Whole breast or chest wall irradiation was delivered in 95.9% (896/934) of patients, adjuvant chemotherapy in 69.5% (644/926), endocrine therapy in 89.6% (673/751) and the proportions were similar in the two arms. The overall rate of positive NSN was 19% (84/442) for patients with cALND. Crude rates of positive NSN according to SN status were 4.5% for ITC (1/22), 9.5% for micro metastases (13/137), 23.9% for macro metastases (61/255) and were respectively 29.36% (64/218), 9.33% (7/75) and 7.94% (10/126) when chemotherapy was administered after cALND, before cALND and for patients without chemotherapy.
The main objective of SERC trial is to demonstrate non inferiority of cALND omission. A strong interaction between timing of cALND and chemotherapy with positive NSN rate was observed.
This study is registered with ClinicalTrials.gov , number NCT01717131 October 19, 2012.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET).
This is a pooled analysis of two multicentre, ...randomised non-comparative phase 2 clinical trials evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer patients: HORGEN (NCT00871858) and CARMINA02 (NCT00629616) studies.
In total, 236 patients were included in CARMINA02 and HORGEN trials. Modified intention-to-treat analysis was available for 217 patients. Median follow-up was 65.2 months. Relapse-free survival (RFS) and overall survival (OS) at 5 years were 83.7% (95% CI: 77.9-88) and 92.7% (95% CI: 88.2-95.6), respectively, with no difference between treatment arms. On univariate analysis, tumour staging (T2 vs T3-4; p = 0.0001), Ki-67 at surgery (≤10% vs >10%; p = 0.0093), pathological tumour size (pT1-2 vs pT3-4; p = 0.0012) and node status (pN negative vs positive; p = 0.007), adjuvant chemotherapy (p = 0.0167) and PEPI score (PEPI group I + II vs III; p = 0.0004) were associated with RFS. No events were observed in patients with pathological response according to the Sataloff classification. Multivariate analysis showed that preoperative endocrine prognostic index (PEPI) group III was associated with significantly worse RFS (p = 0.0069, hazard ratio = 3.33 (95% CI: 1.39-7.98)).
Postmenopausal HR+/HER2- breast cancer patients receiving NET generally have a favourable outcome. The PEPI score identifies a subset of patients of poorer prognosis who are candidates for further additional treatment.
Background
Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75–90% of women. We have previously developed a model including age, complete radiological target excision after ...biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting. –
Methods
Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model.
Results
The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58–0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56–0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77–87%) for all ABL, and 77% (95% CI 71–83%) for patients with ADH. At a 10% threshold, NPV was 89% (84–94%) for all ABL, and 85% (95% CI 78-–92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers.
Conclusion
The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH.
Clinical Trial registration
: NCT02523612.
Background
Results of IBCSG‐23‐01‐trial which included breast cancer patients with involved sentinel nodes (SN) by isolated‐tumor‐cells or micro‐metastases supported the non‐inferiority of completion ...axillary‐lymph‐node‐dissection (cALND) omission. However, current data are considered insufficient to avoid cALND for all patients with SN‐micro‐metastases.
Methods
To investigate the impact of cALND omission on disease‐free‐survival (DFS) and overall survival (OS), we analyzed a cohort of 1421 patients <75 years old with SN‐micro‐metastases who underwent breast conservative surgery (BCS). We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan–Meier estimators representing the experience in the analysis cohort, based on whether all or none had been subject to cALND omission.
Results
Weighted log‐rank tests comparing adjusted Kaplan–Meier survival curves showed significant differences in OS (p‐value = 0.002) and borderline significant differences in DFS (p‐value = 0.090) between cALND omission versus cALND. Cox's regression using stabilized IPTW evidenced an average increase in the risk of death associated with cALND omission (HR = 2.77, CI95% = 1.36–5.66). Subgroup analyses suggest that the rates of recurrence and death associated with cALND omission increase substantially after a large period of time in the half sample of women less likely to miss cALND.
Conclusions
Using IPTW to estimate the causal treatment effect of cALND in a large retrospective cohort, we concluded cALND omission is associated with an increased risk of recurrence and death in women of <75 years old treated by BCS in the absence of a large consensus in favor of omitting cALND. These results are particularly contributive for patients treated by BCS where cALND omission rates increase over time.
To investigate the impact of completion axillary lymph node dissection (ALND) omission in patients with sentinel node micro‐metastases, we retrospectively analyzed a large cohort of 1421 patients with SN micro‐metastases who underwent breast conservative surgery (BCS) in 15 French academic centers. We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan‐Meier estimators representing the experience in the analysis cohort. Weighted log‐rank test comparing adjusted Kaplan‐Meier survival curve showed significant difference for overall survival according to completion axillary lymph node dissection (cALND) or no cALND.
To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer.
A prospective randomized multicentric study was initiated to compare ...the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients.
The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001).
This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.
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