To develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer.
ASCO convened an Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy ...for breast cancer and provide recommended care options.
A total of 41 articles met eligibility criteria and form the evidentiary basis for the guideline recommendations.
Patients undergoing neoadjuvant therapy should be managed by a multidisciplinary care team. Appropriate candidates for neoadjuvant therapy include patients with inflammatory breast cancer and those in whom residual disease may prompt a change in therapy. Neoadjuvant therapy can also be used to reduce the extent of local therapy or reduce delays in initiating therapy. Although tumor histology, grade, stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) expression should routinely be used to guide clinical decisions, there is insufficient evidence to support the use of other markers or genomic profiles. Patients with triple-negative breast cancer (TNBC) who have clinically node-positive and/or at least T1c disease should be offered an anthracycline- and taxane-containing regimen; those with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy. Carboplatin may be offered to patients with TNBC to increase pathologic complete response. There is currently insufficient evidence to support adding immune checkpoint inhibitors to standard chemotherapy. In patients with hormone receptor (HR)-positive (HR-positive), HER2-negative tumors, neoadjuvant chemotherapy can be used when a treatment decision can be made without surgical information. Among postmenopausal patients with HR-positive, HER2-negative disease, hormone therapy can be used to downstage disease. Patients with node-positive or high-risk node-negative, HER2-positive disease should be offered neoadjuvant therapy in combination with anti-HER2-positive therapy. Patients with T1aN0 and T1bN0, HER2-positive disease should not be routinely offered neoadjuvant therapy.Additional information is available at www.asco.org/breast-cancer-guidelines.
Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but ...complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we use single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produces one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides insights into the cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer.
To convene a multidisciplinary panel of breast experts to examine the relationship between margin width and ipsilateral breast tumor recurrence (IBTR) and develop a guideline for defining adequate ...margins in the setting of breast conserving surgery and adjuvant radiation therapy.
A multidisciplinary consensus panel used a meta-analysis of margin width and IBTR from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus.
Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a 2-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component.
The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.
IMPORTANCE: Management of the primary tumor site in patients with metastatic breast cancer remains controversial. OBJECTIVE: To evaluate the patterns of receipt of initial breast surgery for female ...patients with stage IV breast cancer in the United States, with particular attention to women who survived at least 10 years. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) program. Female patients diagnosed as having stage IV breast cancer between 1988 and 2011 and who did not receive radiation therapy as part of the first course of treatment were included (N = 21 372). Kaplan-Meier estimates of median survival and descriptive statistics were used to compare patient and tumor characteristics by receipt of breast surgery at diagnosis. A Royston-Parmar survival model and logistic regression analysis assessed demographic and clinical factors associated with survival and prolonged survival (of at least 10 years). MAIN OUTCOMES AND MEASURES: Differences in survival, particularly survival of at least 10 years, by receipt of initial surgery to the primary tumor. RESULTS: Among the 21 372 patients, the median survival increased from 20 months (1988-1991) to 26 months (2007-2011). During this time, the rate of surgery declined (odds ratio OR, 0.16; 95% CI, 0.12-0.21). Even so, receipt of surgery was associated with improved survival in multivariate analysis, which controlled for patient and clinical characteristics, along with time period (hazard ratio, 0.60; 95% CI, 0.57-0.63). For women diagnosed as having cancer before 2002 (n = 7504), survival of at least 10 years was seen in 9.6% (n = 353) and 2.9% (n = 107) of those who did and did not receive surgery, respectively (OR, 3.61; 95% CI, 2.89-4.50). In multivariate analysis, survival of at least 10 years was associated with receipt of surgery (odds ratio, 2.80; 95% CI, 2.08-3.77), hormone receptor–positive disease (OR, 1.76; 95% CI, 1.25-2.48), older age (OR, 0.41; 95% CI, 0.32-0.54), larger tumor size (OR, 0.37; 95% CI, 0.27-0.51), marital status of being separated at the time of diagnosis (OR, 0.67; 95% CI, 0.51-0.88), and more recent year of diagnosis (OR, 1.43; 95% CI, 1.02-1.99). CONCLUSIONS AND RELEVANCE: Survival in stage IV breast cancer has improved and is increasingly of prolonged duration, particularly for some women undergoing initial breast surgery. As systemic therapy advances provide better control of distant disease in stage IV breast cancer, and as women present with lower distant disease burdens, these findings on initial surgery to the primary tumor may be of importance.
•Integration of clinical notes, concept identifiers and structural clinical features improves the performance of distant breast cancer recurrence prediction using Machine Learning and yields high AUC ...of over 0.88.•Knowledge-guided convolutional neural network outperforms conventional Machine Learning configurations on the task of distant breast cancer recurrence prediction and yields high f1 score of 0.50.•Natural Language Processing techniques, including Bag-of-Word, Metamap, word and entity embedding are employed to represent progress notes and pathology reports.•Detailed report review and error analysis detect common caveats of using clinical notes for prediction of cancer recurrence which could inspire future investments.
Distant recurrence of breast cancer results in high lifetime risks and low 5-year survival rates. Early prediction of distant recurrent breast cancer could facilitate intervention and improve patients’ life quality. In this study, we designed an EHR-based predictive model to estimate the distant recurrent probability of breast cancer patients. We studied the pathology reports and progress notes of 6,447 patients who were diagnosed with breast cancer at Northwestern Memorial Hospital between 2001 and 2015. Clinical notes were mapped to Concept unified identifiers (CUI) using natural language processing tools. Bag-of-words and pre-trained embedding were employed to vectorize words and CUI sequences. These features integrated with clinical features from structured data were downstreamed to conventional machine learning classifiers and Knowledge-guided Convolutional Neural Network (K-CNN). The best configuration of our model yielded an AUC of 0.888 and an F1-score of 0.5. Our work provides an automated method to predict breast cancer distant recurrence using natural language processing and deep learning approaches. We expect that through advanced feature engineering, better predictive performance could be achieved.
Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve ...overall survival (OS), but clinical trials have reported conflicting results.
Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments.
Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52;
= .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3%
39.8%;
< .001). Quality-of-life measures were largely similar between arms.
Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.
Human acellular dermal matrix has become an increasingly used adjunct to traditional submuscular tissue expander/implant breast reconstruction, but there is no strong consensus regarding complication ...outcomes. This study stratified outcomes based on a meta-analysis of complications.
A query of the MEDLINE database for articles on human acellular dermal matrix and submuscular tissue expander breast reconstruction yielded 901 citations. Two levels of screening identified 48 relevant studies. The DerSimonian and Laird random-effects model was used to perform the meta-analysis. Risk ratios and pooled complication rates were calculated for each outcome of interest.
Nineteen studies reporting human acellular dermal matrix (n = 2037) and 35 reporting submuscular outcomes (n = 12,847) were used to estimate complication rates. Rates were generally higher in acellular dermis patients: total complications, 15.4 versus 14.0 percent; seroma, 4.8 versus 3.5 percent; infection, 5.3 versus 4.7 percent; and flap necrosis, 6.9 versus 4.9 percent. Six studies reporting both acellular dermis and submuscular outcomes were used to estimate relative risks. There was an increased risk of total complications (relative risk, 2.05; 95 percent CI, 1.55 to 2.70), seroma (relative risk, 2.73; 95 percent CI, 1.67 to 4.46), infection (relative risk, 2.47; 95 percent CI, 1.71 to 3.57), and reconstructive failure (relative risk, 2.80; 95 percent CI, 1.76 to 4.45) in acellular dermis patients.
The meta-analysis suggests that the use of human acellular dermal matrix increases complication rates vis-à-vis submuscular expander/implant reconstruction. This must be weighed against its reported advantages in enhancing cosmesis and ameliorating contracture.
: Therapeutic, III.
Identifying local recurrences in breast cancer from patient data sets is important for clinical research and practice. Developing a model using natural language processing and machine learning to ...identify local recurrences in breast cancer patients can reduce the time-consuming work of a manual chart review.
We design a novel concept-based filter and a prediction model to detect local recurrences using EHRs. In the training dataset, we manually review a development corpus of 50 progress notes and extract partial sentences that indicate breast cancer local recurrence. We process these partial sentences to obtain a set of Unified Medical Language System (UMLS) concepts using MetaMap, and we call it positive concept set. We apply MetaMap on patients' progress notes and retain only the concepts that fall within the positive concept set. These features combined with the number of pathology reports recorded for each patient are used to train a support vector machine to identify local recurrences.
We compared our model with three baseline classifiers using either full MetaMap concepts, filtered MetaMap concepts, or bag of words. Our model achieved the best AUC (0.93 in cross-validation, 0.87 in held-out testing).
Compared to a labor-intensive chart review, our model provides an automated way to identify breast cancer local recurrences. We expect that by minimally adapting the positive concept set, this study has the potential to be replicated at other institutions with a moderately sized training dataset.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tamoxifen, the prototypic medication for breast cancer prevention, was approved for this purpose by the FDA in 1998. Other drugs have been proven to be effective in the ensuing decades. But the two ...major limitations of these have become clear over time: a lack of protection against hormone receptor-negative breast cancer, and a profile of safety and tolerability that is unacceptable to the majority of women at increased breast cancer risk. Recent preclinical data on targeting of the key oncogenic pathway of PI3K/AKT/mTOR signaling with drugs such as rapamycin and everolimus are provocative. Their efficacy signal should be pursued with further research, but their safety and tolerability profiles remain a concern. See related article by Mazumdar et al., p. 791.
Genetic information is becoming more readily available and is increasingly being used to predict patient cancer types as well as their subtypes. Most classification methods thus far utilize somatic ...mutations as independent features for classification and are limited by study power. We aim to develop a novel method to effectively explore the landscape of genetic variants, including germline variants, and small insertions and deletions for cancer type prediction.
We proposed DeepCues, a deep learning model that utilizes convolutional neural networks to unbiasedly derive features from raw cancer DNA sequencing data for disease classification and relevant gene discovery. Using raw whole-exome sequencing as features, germline variants and somatic mutations, including insertions and deletions, were interactively amalgamated for feature generation and cancer prediction. We applied DeepCues to a dataset from TCGA to classify seven different types of major cancers and obtained an overall accuracy of 77.6%. We compared DeepCues to conventional methods and demonstrated a significant overall improvement (p < 0.001). Strikingly, using DeepCues, the top 20 breast cancer relevant genes we have identified, had a 40% overlap with the top 20 known breast cancer driver genes.
Our results support DeepCues as a novel method to improve the representational resolution of DNA sequencings and its power in deriving features from raw sequences for cancer type prediction, as well as discovering new cancer relevant genes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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