Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we ...compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC.
Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC.
Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates (P < .0001) and 3-year overall survival (OS) rates (P < .0001). TNBC was associated with increased risk for visceral metastases (P = .0005), lower risk for bone recurrence (P = .027), and shorter postrecurrence survival (P < .0001). Recurrence and death rates were higher for TNBC only in the first 3 years. If pCR was achieved, patients with TNBC and non-TNBC had similar survival (P = .24). In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC (P < .0001).
Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival. However, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC, particularly in the first 3 years.
Abstract Purpose To determine the diagnostic performance of Acoustic Radiation Force Impulse (ARFI) Virtual Touch IQ shear wave elastography in the discrimination of benign and malignant breast ...lesions. Materials and methods Conventional B-mode and elasticity imaging were used to evaluate 110 breast lesions. Elastographic assessment of breast tissue abnormalities was done using a shear wave based technique, Virtual Touch IQ (VTIQ), implemented on a Siemens Acuson S3000 ultrasound machine. Tissue mechanical properties were interpreted as two-dimensional qualitative and quantitative colour maps displaying relative shear wave velocity. Wave speed measurements in m/s were possible at operator defined regions of interest. The pathologic diagnosis was established on samples obtained by ultrasound guided core biopsy or fine needle aspiration. Results BIRADS based B-mode evaluation of the 48 benign and 62 malignant lesions achieved 92% sensitivity and 62.5% specificity. Subsequently performed VTIQ elastography relying on visual interpretation of the colour overlay displaying relative shear wave velocities managed similar standalone diagnostic performance with 92% sensitivity and 64.6% specificity. Lesion and surrounding tissue shear wave speed values were calculated and a significant difference was found between the benign and malignant populations (Mann–Whitney U test, p < 0.0001). By selecting a lesion cut-off value of 3.31 m/s we achieved 80.4% sensitivity and 73% specificity. Applying this threshold only to BIRADS 4a masses, we reached overall levels of 92% sensitivity and 72.9% specificity. Conclusion VTIQ qualitative and quantitative elastography has the potential to further characterise B-mode detected breast lesions, increasing specificity and reducing the number of unnecessary biopsies.
To determine whether residual ductal carcinoma in situ (DCIS) after completion of preoperative chemotherapy affects the outcome of patients with histologically defined complete eradication of ...invasive cancer.
Retrospective analysis of a database including 2,302 breast cancer patients treated with neoadjuvant chemotherapy at The University of Texas M.D. Anderson Cancer Center between 1980 and 2004 was performed. The overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were compared for patients with no residual invasive or in situ cancer (pathologic complete response pCR) and patients with no residual invasive cancer but persistent in situ disease (pCR+DCIS).
The mean follow-up time was 250 months. Of the 2,302 treated patients, 78 (3.4%) had pCR, 199 (8.6%) had pCR+DCIS, and 2,025 (88%) had residual invasive cancer. For patients with pCR and pCR+DCIS, the 5-year DFS rates (87.1% in both groups) and 10-year DFS rates (81.3% v 81.7%, respectively) were similar; the 5-year OS rates (91.9% v 92.5%, respectively) and 10-year OS rates (91.8% v 92.5%, respectively) were also similar and significantly better than the rate of patients with residual invasive cancer (74.4%; P < .001). The 5-year locoregional recurrence-free survival rates were also not different between patients with pCR (92.8%; 95% CI, 86.1% to 96.4%) and patients with pCR+DCIS (90.9%; 95% CI, 77.3% to 96.5%; P = .63).
Residual DCIS in patients who experience complete eradication of the invasive cancer in the breast and lymph nodes does not adversely affect survival or local recurrence rate. Inclusion of patients with residual DCIS in the definition of pCR is justified when this outcome is used as an early surrogate for long-term survival.
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.
There is a scarcity of data exploring early breast cancer (eBC) in very young patients. We assessed shared and intrinsic prognostic factors in a large cohort of patients aged ≤35, compared to a ...control group aged 36 to 50.
Patients ≤50 were retrospectively identified from a multicentric cohort of 23,134 eBC patients who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses for DFS and OS were built. To assess the independent impact of age, 1 to 3 case-control analysis was performed by matching ≤35 and 36–50 years patients.
Of 6481 patients, 556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger tumors, higher grade, ER-negativity, macroscopic lymph node involvement (pN + macro), lymphovascular invasion (LVI), mastectomy, and chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with worse DFS HR 1.56, 95% CI 1.32–1.84; p < 0.001, and OS HR 1.29, 95% CI 1.03–1.60; p = 0.025, as were high grade, large tumor, LVI, pN + macro, ER-negativity, period of diagnostic, and absence of ET or CT (for DFS). Adverse prognostic impact of age ≤35 was maintained in the case control-matched analysis for DFS HR 1.56, 95%CI 1.28–1.91, p < 0.001, and OS HR 1.33, 95%CI 1.02–1.73, p = 0.032. When only considering patients ≤35, ER, tumor size, nodal status, and LVI were independently associated with survival in this subgroup.
Age ≤35 is associated with less favorable presentation and more aggressive treatment strategies. Our results support the poor prognosis value of young age, which independently persisted when adjusting for other prognostic factors and treatments.
•Young age is an independent prognostic factor.•Age ≤35 is associated with more severe presentation and more aggressive treatments.•Triple-negative, HER2-positive, and luminal-B subtypes are more common.
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.
The near-infrared (NIR) fluorescence axillary reverse mapping (ARM) procedure is a promising tool to identify and preserve arm lymphatic drainage during axillary lymph node dissection (ALND). The ...ARMONIC clinical trial was conducted to validate the technique on a large cohort of patients and to analyze the predictive clinical factors for ARM lymph node metastasis. For the first time, the fluorescence signal intensity from the ARM lymph nodes was measured and correlated with clinical findings. A total of 109 patients with invasive breast cancer and indications of mastectomy and ALND underwent the NIR fluorescence ARM procedure. Indocyanine green was administered by intradermal injection followed by intraoperative identification and resection of the ARM lymph nodes with NIR fluorescence camera guidance. The fluorescence signal intensity and signal distribution were then measured ex vivo and compared with clinical outcomes. ARM lymph nodes were successfully identified by fluorescence in 94.5% of cases. The mean normalized fluorescence signal intensity value was 0.47 with no significant signal difference between metastatic and non-metastatic ARM lymph nodes (
= 0.3728). At the microscopic level, the fluorescence signal distribution was focally intense in lymphoid tissue areas. Only the preoperative diagnosis of metastasis in the axillary nodes of patients was significantly associated with a higher ARM node fluorescence signal intensity (
= 0.0253), though it was not significantly associated with the pathological nodal (pN) status (
= 0.8081). Based on an optimal cut-off fluorescence value, the final sensitivity and specificity of the NIR fluorescence ARM procedure for ARM lymph node metastatic involvement were 64.7% and 47.3%, respectively. Although our preliminary results did not show that fluorescence signal intensity is a reliable diagnostic tool, the NIR fluorescence ARM procedure may be useful for ARM lymph node identification. Clinical trial registration: NCT02994225.
The clinical outcome for patients with breast cancer is influenced by the metastatic competence of the cancer and its sensitivity to endocrine therapy and chemotherapy. A molecular marker may be ...prognostic of outcome or predictive of response to therapy, or a combination of both.
We examined separately the prognostic and predictive values of tau mRNA expression in estrogen receptor (ER)-positive primary breast cancers in three patient cohorts. We used gene expression data from 209 untreated patients to assess the pure prognostic value of tau, data from 267 patients treated with adjuvant tamoxifen to assess predictive value for endocrine therapy, and data from 82 patients treated with preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide (paclitaxel/FAC) to assess predictive value for chemotherapy response. Wilcoxon rank sum test was used to compare tau expression between different outcome groups.
Higher tau mRNA expression showed borderline nonsignificant association with better prognosis in the absence of systemic adjuvant therapy. Higher tau mRNA expression was significantly associated with no recurrence (at 5 and 10 years, P = 0.005 and P = 0.05, respectively) in patients treated with tamoxifen, indicating a predictive value for endocrine therapy. Tau expression was significantly lower in patients who achieved pathologic complete response to paclitaxel/FAC chemotherapy (P < 0.001).
This study suggests that high tau mRNA expression in ER-positive breast cancer indicates an endocrine-sensitive but chemotherapy-resistant disease. In contrast, low tau expression identifies a subset of ER-positive cancers that have poor prognosis with tamoxifen alone and may benefit from taxane-containing chemotherapy.
Abstract Background Axillary lymphadenectomy for primary breast cancer produces a non negligible rate of postoperative lymphorrhea, prolonged hospital stays and multiple seroma punctures. We ...evaluated the impact of low-thrombin fibrin sealant glue on surgical wounds in patients undergoing axillary lymph node dissection for breast cancer. Methods We conducted an observational study of 149 patients who underwent axillary lymphadenectomy for primary breast cancer between January 2014 and December 2015. Data were obtained from two successive prospective studies. The hospital stay length and morbidity (seromas, punctures) were compared between two groups: patients who had padding sutures and low-thrombin fibrin sealant glue without drainage (N=49) and patients with drainage alone (N=100). Hospital costs were assessed from the hospital perspective. Results The mean hospital stay length was shorter in the fibrin sealant group (2.6 vs. 4.7 days; p < 0.001). Seroma magnitude and punctures were similar in patients treated with fibrin sealant compared to patients with drainage alone. The rate of needle aspiration for seroma was similar irrespective of whether or not a drain or fibrin sealant was used (30.6% vs 33%, p = 0 .77). Conclusion Low-thrombin fibrin sealant glue does not significantly reduce the amount of fluid produced in the axilla after breast surgery. However its systematic use may help reduce hospital stays and costs.
The aim of this study was to assess the efficacy (response rate centered on 80%) of a somatostatin analog with high affinity for 4 somatostatin receptors in reducing the postoperative incidence of ...symptomatic lymphocele formation following total mastectomy with axillary lymph node dissection.
This prospective, double-blind, randomised, placebo-controlled, phase 2 trial was conducted in two secondary care centres.
All female patients for whom mastectomy and axillary lymph node dissection were indicated were eligible for the study, including patients who had received neo-adjuvant chemotherapy. Main exclusion criteria were related to diabetes, cardiac insufficiency, disorder of cardiac conduction or hepatic failure.
Patients were randomised to receive one injection of either prolonged-release pasireotide 60 mg or placebo (physiological serum), which were administered intramuscularly 7 to 10 days before the scheduled surgery. The study was conducted in a double-blind manner.
The primary outcome measure was the percentage of patients who did not develop post-operative axillary symptomatic lymphoceles during the 2 postoperative months. Secondary endpoints were the total quantity of lymph drained, duration and daily volume of drainage and aspirated volumes of lymph.
Ninety-one patients were randomised. Ninety patients were evaluable: 42 patients received pasireotide, and 48 patients received placebo. The mean estimated response rate were 62.4% (95% Credibility Interval CrI: 48.6%-75.3%) in the treatment group and 50.2% (95% CrI: 37.6%-62.8%) in the placebo group. Overall safety was comparable across groups, and one serious adverse event occurred. In the treatment group, one patient with known insulin-depe*ndent diabetes required hospitalization for hyperglycaemia.
With this phase 2 preliminary study, even if our results indicate a trend towards a reduction in symptomatic lymphocele, pre-operative injection of pasireotide failed to achieve a response rate centered on 80%. Pharmacokinetics analysis suggests that effect of pasireotide could be optimised.
ClinicalTrials.gov NCT01356862.
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