Concept: Mammary ductal carcinoma
Women with ductal carcinoma in situ (DCIS), or stage 0 breast cancer, often experience a second primary breast cancer (DCIS or invasive), and some ultimately die of breast cancer.
Background Routine resection of cavity shave margins (additional tissue circumferentially around the cavity left by partial mastectomy) may reduce the rates of positive margins (margins positive for tumor) and reexcision among patients undergoing partial mastectomy for breast cancer. Methods In this randomized, controlled trial, we assigned, in a 1:1 ratio, 235 patients with breast cancer of stage 0 to III who were undergoing partial mastectomy, with or without resection of selective margins, to have further cavity shave margins resected (shave group) or not to have further cavity shave margins resected (no-shave group). Randomization occurred intraoperatively after surgeons had completed standard partial mastectomy. Positive margins were defined as tumor touching the edge of the specimen that was removed in the case of invasive cancer and tumor that was within 1 mm of the edge of the specimen removed in the case of ductal carcinoma in situ. The rate of positive margins was the primary outcome measure; secondary outcome measures included cosmesis and the volume of tissue resected. Results The median age of the patients was 61 years (range, 33 to 94). On final pathological testing, 54 patients (23%) had invasive cancer, 45 (19%) had ductal carcinoma in situ, and 125 (53%) had both; 11 patients had no further disease. The median size of the tumor in the greatest diameter was 1.1 cm (range, 0 to 6.5) in patients with invasive carcinoma and 1.0 cm (range, 0 to 9.3) in patients with ductal carcinoma in situ. Groups were well matched at baseline with respect to demographic and clinicopathological characteristics. The rate of positive margins after partial mastectomy (before randomization) was similar in the shave group and the no-shave group (36% and 34%, respectively; P=0.69). After randomization, patients in the shave group had a significantly lower rate of positive margins than did those in the no-shave group (19% vs. 34%, P=0.01), as well as a lower rate of second surgery for margin clearance (10% vs. 21%, P=0.02). There was no significant difference in complications between the two groups. Conclusions Cavity shaving halved the rates of positive margins and reexcision among patients with partial mastectomy. (Funded by the Yale Cancer Center; ClinicalTrials.gov number, NCT01452399 .).
With the increasing ability to routinely and rapidly digitize whole slide images with slide scanners, there has been interest in developing computerized image analysis algorithms for automated detection of disease extent from digital pathology images. The manual identification of presence and extent of breast cancer by a pathologist is critical for patient management for tumor staging and assessing treatment response. However, this process is tedious and subject to inter- and intra-reader variability. For computerized methods to be useful as decision support tools, they need to be resilient to data acquired from different sources, different staining and cutting protocols and different scanners. The objective of this study was to evaluate the accuracy and robustness of a deep learning-based method to automatically identify the extent of invasive tumor on digitized images. Here, we present a new method that employs a convolutional neural network for detecting presence of invasive tumor on whole slide images. Our approach involves training the classifier on nearly 400 exemplars from multiple different sites, and scanners, and then independently validating on almost 200 cases from The Cancer Genome Atlas. Our approach yielded a Dice coefficient of 75.86%, a positive predictive value of 71.62% and a negative predictive value of 96.77% in terms of pixel-by-pixel evaluation compared to manually annotated regions of invasive ductal carcinoma.
By rationally designing a functional molecular probe with high sequence specificity and taking the advantages of sensitive isothermal amplification with simple operation, we develop a one-pot hairpin-mediated quadratic enzymatic amplification (HQEA) strategy for microRNA (miRNA) detection. Our method exhibits ultra-high sensitivity toward the miR-21 with a detection limit of 10 fM at 37 ºC and 1 aM at 4 ºC that corresponds to 9 strands of miR-21 in a 15 µL sample, and is capable of distinguishing among miRNA family members. More importantly, the proposed approach is also sensitive and selective when apply it in crude extrac-tions from MCF-7, PC3 cell lines, and even patient tissues from intraductal carcinoma and invasive ductal carcinoma of the breast.
Although epidemiological studies propose aggressive and non-aggressive forms of ductal carcinoma in situ (DCIS), they cannot be identified with conventional histopathology. We now report a retrospective study of human biopsy samples using biomarker ratio imaging microscopy (BRIM). Using BRIM, micrographs of biomarkers whose expression correlates with breast cancer aggressiveness are divided by micrographs of biomarkers whose expression negatively correlates with aggressiveness to create computed micrographs reflecting aggressiveness. The biomarker pairs CD44/CD24, N-cadherin/E-cadherin, and CD74/CD59 stratified DCIS samples. BRIM identified subpopulations of DCIS lesions with ratiometric properties resembling either benign fibroadenoma or invasive carcinoma samples. Our work confirms the existence of distinct subpopulations of DCIS lesions, which will likely have utility in breast cancer research and clinical practice.
Despite the widespread use of bras among U.S. women and concerns in the lay media that bra wearing may increase breast cancer risk, there is a scarcity of credible scientific studies addressing this issue. The goal of the study was to evaluate the relationship between various bra-wearing habits and breast cancer risk among postmenopausal women. We conducted a population-based case-control study of breast cancer in the Seattle-Puget Sound metropolitan area that compared 454 invasive ductal carcinoma (IDC) cases and 590 invasive lobular carcinoma (ILC) cases diagnosed between 2000 and 2004 with 469 control women between 55 to 74 years of age. Information on bra-wearing habits and other breast cancer risk factors was collected from study participants through in-person interviews. Multivariate adjusted odds ratios (OR) and their associated 95% confidence intervals (CI) were estimated using polytomous logistic regression. No aspect of bra wearing, including bra cup size, recency, average number of hours/day worn, wearing a bra with an underwire, or age first began regularly wearing a bra, was associated with risks of either IDC or ILC. Our results did not support an association between bra wearing and increased breast cancer risk among postmenopausal women. Cancer Epidemiol Biomarkers Prev; 1-5. ©2014 AACR.
Purpose To investigate whether specific imaging features on breast magnetic resonance (MR) images are associated with ductal carcinoma in situ (DCIS) recurrence risk after definitive treatment. Materials and Methods Patients with DCIS who underwent preoperative dynamic contrast material-enhanced (DCE) MR imaging between 2004 and 2014 with ipsilateral recurrence more than 6 months after definitive surgical treatment were retrospectively identified. For each patient, a control subject with DCIS that did not recur was identified and matched on the basis of clinical, histopathologic, and treatment features known to affect recurrence risk. On DCE MR images, lesion characteristics (longest diameter, functional tumor volume [FTV], peak percentage enhancement [PE], peak signal enhancement ratio [SER], and washout fraction) and normal tissue features (background parenchymal enhancement [BPE] volume, mean BPE) were quantitatively measured. MR imaging features were compared between patients and control subjects by using the Wilcoxon signed-rank test, with adjustment for multiple comparisons. Results Of 415 subjects with DCIS who underwent preoperative MR imaging, 14 experienced recurrence and 11 had an identifiable matching control subject (final cohort, 11 patients and 11 control subjects). Median time to recurrence was 14 months, and median follow-up for control subjects was 102 months. When compared with matched control subjects, patients with DCIS recurrence exhibited significantly greater FTV (median, 9.3 cm(3) vs 1.3 cm(3), P = .01), lesion peak SER (median, 1.7 vs 1.2; P = .03), and mean BPE (median, 58.3% vs 41.1%; P = .02). Conclusion Quantitative lesion and normal breast tissue characteristics at preoperative MR imaging in women with newly diagnosed DCIS show promise for association with breast cancer recurrence after treatment. (©) RSNA, 2017.
The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with ½/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18-30, and ≥ 31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated (n = 27) and 2.9% in chemotherapy-untreated patients (n = 352); P = 0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients (n = 102) was significantly lower than in untreated patients (n = 156) (1.0% vs. 9.7% P = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n = 89) and 4.4% in chemotherapy-untreated patients (n = 488); P = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1-3 positive nodes and Recurrence Score < 18.
The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 (n = 304) and 11-25 (n = 1037) (TAILORx categorization) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.
Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections. We applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions in addition to exome sequencing. Our data reveal a direct genomic lineage between in situ and invasive tumor subpopulations and further show that most mutations and copy number aberrations evolved within the ducts prior to invasion. These results support a multiclonal invasion model, in which one or more clones escape the ducts and migrate into the adjacent tissues to establish the invasive carcinomas.