Context.—
Pathologic tumor size is significant in the treatment of breast carcinoma and is routinely measured on excision.
Objective.—
To analyze the need for measuring size of invasive mammary ...carcinoma on biopsy.
Design.—
Nine hundred twenty-two cases of invasive carcinoma whose size was measured (greatest linear measurement) on biopsy and excision was correlated, including imaging when available (110 cases).
Results.—
Patient mean age was 62 years. Most (90%; 830 of 922) carcinomas were ductal and sampled by ultrasound and graded as follows: well, 13% (113 of 922); moderately, 58% (532 of 922), and poorly differentiated, 28% (258 of 922); 19 microinvasive not graded. Tumor mean size was 7.5 mm on biopsy and 14.4 mm on excision. Biopsy modality was as follows: ultrasound, 7.8 mm (92%, 844 of 922); mammotome, 3.3 mm (7%, 65 of 922); and magnetic resonance imaging, 5.9 mm (1%, 13 of 922). Size comparison on biopsy versus excision was biopsy > excision: 8% (72 of 922), biopsy = excision: 10% (95 of 922), and biopsy < excision: 82% (755 of 922). Half (36 of 72) of the biopsy > excision tumors were less than 5 mm, 96% (726 of 755) of biopsy < excision tumors were greater than 5 mm, while those equal on both were predominantly (88%, 84 of 95) less than 10 mm, 20% (19 of 95) of which were microinvasive. Stage changed in 600 cases, staging based on excision in 581 (63%), and staging based on biopsy in 19 (2%). Radiologic-pathologic correlation (n = 110) showed perfect concordance in 11 (10%), 83 (75%) were ±1 to 2 mm, and 16 (15%) were ± more than 3 mm. Difference between the biopsy and excision ranged from a lower limit of 1.3 mm for T1a tumors to 18 mm for T2.
Conclusions.—
While most carcinomas are larger on excision, 18% (167 of 922) are larger or equal on biopsy. Factors predictive of biopsy > excision tumors include stage 1 tumors (P < .001), especially less than 5 mm, and sampled by mammotome. We recommend measuring invasive carcinoma on biopsy and excision.
Pathologic tumor size is significant in the treatment of breast carcinoma and is routinely measured on excision.
To analyze the need for measuring size of invasive mammary carcinoma on biopsy.
Nine ...hundred twenty-two cases of invasive carcinoma whose size was measured (greatest linear measurement) on biopsy and excision was correlated, including imaging when available (110 cases).
Patient mean age was 62 years. Most (90%; 830 of 922) carcinomas were ductal and sampled by ultrasound and graded as follows: well, 13% (113 of 922); moderately, 58% (532 of 922), and poorly differentiated, 28% (258 of 922); 19 microinvasive not graded. Tumor mean size was 7.5 mm on biopsy and 14.4 mm on excision. Biopsy modality was as follows: ultrasound, 7.8 mm (92%, 844 of 922); mammotome, 3.3 mm (7%, 65 of 922); and magnetic resonance imaging, 5.9 mm (1%, 13 of 922). Size comparison on biopsy versus excision was biopsy > excision: 8% (72 of 922), biopsy = excision: 10% (95 of 922), and biopsy < excision: 82% (755 of 922). Half (36 of 72) of the biopsy > excision tumors were less than 5 mm, 96% (726 of 755) of biopsy < excision tumors were greater than 5 mm, while those equal on both were predominantly (88%, 84 of 95) less than 10 mm, 20% (19 of 95) of which were microinvasive. Stage changed in 600 cases, staging based on excision in 581 (63%), and staging based on biopsy in 19 (2%). Radiologic-pathologic correlation (n = 110) showed perfect concordance in 11 (10%), 83 (75%) were ±1 to 2 mm and 16 (15%) were ± more than 3 mm. Difference between the biopsy and excision ranged from a lower limit of 1.3 mm for T1a tumors to 18 mm for T2.
While most carcinomas are larger on excision, 18% (167 of 922) are larger or equal on biopsy. Factors predictive of biopsy > excision tumors include stage 1 tumors (P < .001), especially less than 5 mm, and sampled by mammotome. We recommend measuring invasive carcinoma on biopsy and excision.
Transient, multi-protein complexes are important facilitators of cellular functions. This includes the chaperome, an abundant protein family comprising chaperones, co-chaperones, adaptors, and ...folding enzymes-dynamic complexes of which regulate cellular homeostasis together with the protein degradation machinery. Numerous studies have addressed the role of chaperome members in isolation, yet little is known about their relationships regarding how they interact and function together in malignancy. As function is probably highly dependent on endogenous conditions found in native tumours, chaperomes have resisted investigation, mainly due to the limitations of methods needed to disrupt or engineer the cellular environment to facilitate analysis. Such limitations have led to a bottleneck in our understanding of chaperome-related disease biology and in the development of chaperome-targeted cancer treatment. Here we examined the chaperome complexes in a large set of tumour specimens. The methods used maintained the endogenous native state of tumours and we exploited this to investigate the molecular characteristics and composition of the chaperome in cancer, the molecular factors that drive chaperome networks to crosstalk in tumours, the distinguishing factors of the chaperome in tumours sensitive to pharmacologic inhibition, and the characteristics of tumours that may benefit from chaperome therapy. We find that under conditions of stress, such as malignant transformation fuelled by MYC, the chaperome becomes biochemically 'rewired' to form a network of stable, survival-facilitating, high-molecular-weight complexes. The chaperones heat shock protein 90 (HSP90) and heat shock cognate protein 70 (HSC70) are nucleating sites for these physically and functionally integrated complexes. The results indicate that these tightly integrated chaperome units, here termed the epichaperome, can function as a network to enhance cellular survival, irrespective of tissue of origin or genetic background. The epichaperome, present in over half of all cancers tested, has implications for diagnostics and also provides potential vulnerability as a target for drug intervention.
Background
Currently, positive margins at lumpectomy contribute to health care cost, patient anxiety, and treatment delay. Multiple technology solutions are being explored with the aim of lowering ...re‐excision rates for breast‐conserving surgery (BCS). We examined wide‐field optical coherence tomography (WF‐OCT), an innovative adjunct intraoperative imaging tool for tissue visualization of margins.
Methods
This IRB‐approved pilot study included women with invasive or in situ carcinoma scheduled for primary BCS. Lumpectomy specimens and any final/revised margins were imaged by optical coherence tomography immediately prior to standard histological processing. The optical coherence tomography used provided two‐dimensional, cross‐sectional, real‐time depth visualization of the margin widths around excised specimens. A volume of images was captured for 10 × 10 cm tissue surface at high resolution (sub‐30 μm) to a depth of 2 mm. Integrated interpretation was performed incorporating final pathology linked with the optical image data for correlation.
Results
Wide‐field optical coherence tomography was performed on 185 tissue samples (50 lumpectomy specimens and 135 additional margin shaves) in 50 subjects. Initial diagnosis was invasive ductal carcinoma (IDC) in 10, ductal carcinoma in situ (DCIS) in 14, IDC/DCIS in 22, invasive lobular carcinoma (ILC) in 2, ILC/DCIS in 1, and sarcoma in 1. Optical coherence tomography was concordant with final pathology in 178/185 tissue samples for overall accuracy of 86% and 96.2% (main specimen alone and main specimen + shave margins). Of seven samples that were discordant, 57% (4/7) were considered close (DCIS < 2 mm from margin) per final pathology.
Conclusion
Wide‐field optical coherence tomography demonstrated concordance with histology at tissue margins, supporting its potential for use as a real‐time adjunct intraoperative imaging tool for margin assessment. Further studies are needed for comprehensive evaluation in the intraoperative setting.
Improved imaging and neoadjuvant chemotherapy (NAT) have led to higher pathologic complete response rates (pCR) in patients with invasive breast cancer. This has questioned the necessity of surgery ...and axillary lymph node (ALN) dissection in these patients. Prospective clinical trials are implementing extensive core biopsies of the tumor bed of patients with clinical complete response as a means to identify and spare them breast surgery. In addition, it is anticipated that patients with pCR are most likely going to have no or minimal disease in ALN as well. To verify the feasibility of these trials, we performed a pathologic analysis of all our patients who have undergone NAT from 2009 to present. Using pathology data base, we identified 362 patients treated with neoadjuvant chemotherapy followed by surgery. Clinical and pathologic information including gross and microscopic descriptions as well as biomarker status was collected. pCR was 50% for patients with negative ALN pretreatment but only 28% for patients with positive ALN at diagnosis. Despite achieving pCR in the breast, up to 10% of patients with positive ALN and 1% with negative ALN had persistent disease. Eight percent of patients that were presumed to have no ALN disease either clinically and or by imaging were found to have metastatic carcinoma in ALN. The metastases were predominantly (80%) <5 mm, and not palpable on physical examination and or due to biopsy sampling error. pCR in breast and ALN directly correlated with tumor size, ALN disease, and Her2 positive and triple negative receptor phenotype. In breast cancer patients who are node positive at time of diagnosis with pCR in the breast after neoadjuvant chemotherapy, residual lymph node disease was very uncommon. Further study is warranted to select patients who may avoid breast and axillary surgery post neoadjuvant chemotherapy.
Purpose Breast fibroglandular tissue (FGT), as visualized on a mammogram (mammographic density, MD), is one of the strongest known risk factors for breast cancer. FGT is also visible on breast MRI, ...and increased background parenchymal enhancement (BPE) in the FGT has been identified as potentially a major breast cancer risk factor. The aim of this exploratory study was to examine the biologic basis of BPE. Methods We examined the unaffected contra-lateral breast of 80 breast cancer patients undergoing a prophylactic mastectomy before any treatment other than surgery of their breast cancer. BPE was classified on the BI-RADS scale (minimal/mild/moderate/marked). Slides were stained for microvessel density (MVD), CD34 (another measure of endothelial density), glandular tissue within the FGT and VEGF. Spearman correlations were used to evaluate the associations between BPE and these pathologic variables. Results In pre-menopausal patients, BPE was highly correlated with MVD, CD34 and glandular concentration within the FGT, and the pathologic variables were themselves highly correlated. The expression of VEGF was effectively confined to terminal duct lobular unit (TDLU) epithelium. The same relationships of the four pathologic variables with BPE were seen in post-menopausal patients, but the relationships were much weaker and not statistically significant. Conclusion The strong correlation of BPE and MVD together with the high correlation of MVD with glandular concentration seen in pre-menopausal patients indicates that increased breast cancer risk associated with BPE in pre-menopausal women is likely to result from its association with increased concentration of glandular tissue in the FGT. The effective confinement of VEGF expression to the TDLUs shows that the signal for MVD growth arises directly from the glandular tissue. Further studies are needed to understand the basis of BPE in post-menopausal women.
F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (
F-fluciclovine) is a leucine analog radiotracer that depicts amino acid transport into cells.
F-fluciclovine PET/CT visualizes malignancy, ...including prostate cancer, invasive ductal breast cancer, and invasive lobular breast cancer. Whether changes in
F-fluciclovine avidity reflect changes in tumor burden resulting from treatment has not been shown. In this prospective clinical trial (clinical trials.gov: NCT01864083), changes in
F-fluciclovine avidity after neoadjuvant therapy were compared to breast cancer therapy response, as determined by residual tumor burden on pathology, were evaluated.
Twenty-four women with a new diagnosis of locally advanced invasive ductal breast cancer (
= 18) or invasive lobular breast cancer (
= 6) underwent
F-fluciclovine PET/CT before and after the completion of neoadjuvant systemic therapy. SUV
, SUV
, metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes on each examination and corrected for background
F-fluciclovine avidity. The relationship between changes in
F-fluciclovine avidity and the percentage of reduction of tumor on pathology was assessed with the Spearman rank correlation.
The median decrease in the corrected SUV
of the primary breast lesions was 99% (range, 33%-100%). The median reduction of tumor on pathology was 92% (range, 10%-100%). Changes in
F-fluciclovine avidity were strongly correlated with the percentage of reduction of tumor on pathology (Spearman ρ, 0.79; 95% CI, 0.56-0.90;
< 0.001).
Changes in
F-fluciclovine avidity strongly correlated with the tumor response on pathology in this pilot study.
The objective of our study was to determine the frequency of cancer at surgery in breast lesions yielding papilloma at MRI-guided 9-gauge vacuum-assisted biopsy (VAB) and to determine whether any ...features are associated with cancer upgrade.
For this study, 1487 MRI-guided vacuum-assisted biopsies performed from January 2004 to March 2011 were reviewed. Lesions yielding papilloma were identified and classified as papilloma with or without atypia. Surgical findings were reviewed to determine the cancer rate. Statistical analysis was performed and 95% CIs were calculated.
Papilloma was identified in 75 of the 1487 MRI-guided vacuum-assisted biopsies (5%). These 75 papillomas occurred in 73 women with a median age of 49 years (age range, 27-70 years). Of the 75 papillomas, 25 (33%) had atypia and 50 (67%) did not on core needle biopsy. Subsequent surgery of 67 of the 75 papillomas (89%) yielded ductal carcinoma in situ (DCIS) in four (6%; 95% CI, 2-15%). Surgery yielded DCIS in two of 23 papillomas with atypia (9%; 95% CI, 1-28%) at MRI-guided VAB and in two of 44 papillomas without atypia (5%; 95% CI, 0.4-16%) at MRI-guided VAB; these cancer rates did not differ significantly (p=0.6). Postmenopausal status (p=0.04) and histologic size of less than 0.2 cm (p=0.04) had a significant association with the cancer upgrade rate.
Papilloma with or without atypia was found in 5% of patients who underwent MRI-guided VAB during the study period. Surgery revealed cancer in 6%. DCIS was found at surgery in 9% of lesions yielding papilloma with atypia versus 5% of lesions yielding papilloma without atypia. For lesions yielding papilloma with or without atypia at MRI-guided VAB, surgical excision is warranted.
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