Lumpectomy Specimens Research Articles

Direct identification of breast cancer pathologies using blind separation of label-free localized reflectance measurements

Breast tumors are blindly identified using Principal (PCA) and Independent Component Analysis (ICA) of localized reflectance measurements. No assumption of a particular theoretical model for the reflectance needs to be made, while the resulting features are proven to have discriminative power of breast pathologies. Normal, benign and malignant breast tissue types in lumpectomy specimens were imaged ex vivo and a surgeon-guided calibration of the system is proposed to overcome the limitations of the blind analysis. A simple, fast and linear classifier has been proposed where no training information is required for the diagnosis. A set of 29 breast tissue specimens have been diagnosed with a sensitivity of 96% and specificity of 95% when discriminating benign from malignant pathologies. The proposed hybrid combination PCA-ICA enhanced diagnostic discrimination, providing tumor probability maps, and intermediate PCA parameters reflected tissue optical properties.

Micro-computed tomography (Micro-CT): a novel approach for intraoperative breast cancer specimen imaging

Intraoperative radiographic examination of breast specimens is commonly performed to confirm excision of image-detected breast lesions, but it is not reliable for assessing margin status. A more accurate method of intraoperative breast specimen imaging is needed. Micro-CT provides quantitative imaging parameters, image rotation, and virtual "slicing" of intact breast specimens. We explored the use of micro-CT for assessment of a variety of clinical breast specimens. Specimens were evaluated with a table top micro-CT scanner, Skyscan 1173 (Skyscan, Belgium), with a 40-130 kV, 8 W X-ray source. Skyscan software for 3D image analysis (Dataviewer and CTVox) was employed to review 3D graphics of specimens. Scanning for 7 min and another 7 min for image reconstruction provided the desired resolution for breast specimens. Breast lumpectomy specimens, shaved cavity margins, mastectomy specimens, and axillary lymph nodes were imaged by micro-CT. The micro-CT images could be rotated in all directions and cross sections of internal portions of specimens could be visualized from any angle. This provided information about spatial orientation of masses and calcifications relative to margins in intact lumpectomy specimens. Micro-CT is a potentially useful tool for assessment of breast cancer specimens, allowing real-time analysis of tumor location in breast lumpectomy specimens or shaved cavity margins. Micro-CT may also be useful for assessing sentinel lymph nodes and mastectomy specimens.

Abstract LB-85: Real-time molecular imaging of cathepsins for rapid detection of cancer in human breast lumpectomy specimens.

Abstract Objectives: Successful breast cancer surgery relies on the rapid and accurate localization of the residual tumor cells/tissues positioned to close to the surface of the lumpectomy specimen. Presence of cancerous cells/tissue inside of the surgical margin may lead to secondary surgeries creating an enormous burden in time, cost and patient anxiety. Recent studies have demonstrated the ability of near infrared fluorescent smart imaging probes to target tumor proteases in small animal models of cancers. These probes are extremely selective, robust, and useful for imaging tumor-expressed proteases in human tumor tissue xenografts implanted in mice. The high target selectivity, cellular permeability, and rapid kinetics have prompted us to utilize these probes to identify cancer at or near the surface of lumpectomy specimens during breast conserving surgeries. Material and Method: To determine the feasibility of using these probes for rapid detection of cancer cells in lumpectomy margins, we characterized the ability of ex vivo topically applied quenched activity based probe, GB119, to: 1) interact with tumor associated proteases; 2) become activated by human breast cancer tissues; 3) penetrate normal human breast tissue; and 4) “find” cancerous tissues residing within normal breast tissues. Results: Specifically we found that: 1) In vitro incubation of GB119 and breast cancer cell lysates resulted in cathepsin-dependent activation of GB119 and fluorescence in 3-6 min; 2) GB119 was activated and accumulated in lysosomes of MCF-7 breast cancer cell culture in vitro; 3) Human breast cancer xenografts could be detected under 2-mm layer of normal breast tissue in 5-10 min by topical application of GB119 onto the breast tissue indicating high levels of permeability of the normal breast tissue for the probe. The broad-spectrum suicide cysteine protease inhibitor K11777 abrogated the ability of the probe to detect breast cancer xenograft implying a high specificity of the GB119/cathepsin-dependent fluorescent signal. 4) IHC analysis confirmed the presence of GB119’s fluorochrome, Cy5, both at the surface and inside (up to 1-mm) of the breast cancer xenograft which was separated from the probe by 2-mm layer of the normal breast tissue. 5) Pathology data confirm that GB119/tumor cathepsin-dependent fluorescence on the surface of the human lumpectomy specimens pretreated with GB119 correlates with presence of breast cancer in surgical margin. Conclusions: Topical application of GB119 onto surgically removed lumpectomy specimens may be a new tool to rapidly and completely assess cancer infiltrates in the lumpectomy margins essential to improve outcomes for breast cancer patients. Citation Format: Eugene Vykhovanets, Hannah Gilmore, Galia Blum, Matthew Bogyo, James Basilion. Real-time molecular imaging of cathepsins for rapid detection of cancer in human breast lumpectomy specimens. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-85. doi:10.1158/1538-7445.AM2013-LB-85

Does the volume of ductal carcinoma in situ impact the positive margin rate in patients undergoing breast conservation for invasive breast cancer?

BackgroundWe sought to investigate whether the volume of ductal carcinoma in situ (DCIS) impacts margin status in patients undergoing lumpectomy for invasive breast cancer. MethodsWe identified 358 patients with stages I–III invasive breast cancer and associated DCIS who were treated with breast-conserving therapy from 1999 to 2009. Data included patient and tumor characteristics, percentage of DCIS (<25%, 26%–50%, or >50%), and pathologic outcomes. Data were compared using chi-square and Fisher exact tests. A two-tailed P value of <0.05 was considered significant. ResultsThe 358 patients had a mean age of 58 ± 13 y; 260 (72%) patients were >50 y. The volume of DCIS in lumpectomy specimens was <25% in 296 (83%) patients, 26%–50% in 29 (8%) patients, and >50% in 33 (9%) patients. Tumors with decreasing DCIS volume were more likely to be estrogen receptor positive (239 [82%] with <25% DCIS, 21 [72%] with 26%–50% DCIS, 22 [67%] with >50% DCIS; P=0.026). DCIS volume was not significantly associated with patient age, tumor size, grade, and stage, nodal status, progesterone receptor status, or Her2 status (P>0.05). Overall, 137 (38%) patients had one or more positive margins, including 97 of 296 (33%) with <25% DCIS volume, 17 of 29 (59%) with 26%–50% DCIS volume, and 23 of 33 (70%) with >50% DCIS volume (P<0.0001). ConclusionsThe volume of DCIS associated with an invasive breast cancer in the final lumpectomy specimen is a strong predictor of positive surgical margins. Future analyses will focus on the ability of core pathology to provide this information for intraoperative surgical decision making.

Using therapeutic mammoplasty to extend the role of breast-conserving surgery in women with larger or ptotic breasts

The equivalence of breast-conserving surgery followed by postoperative radiotherapy against mastectomy is now firmly established in patients with early breast cancer. The results of surgery in large-breasted women can be poor, with radiation-induced fibrosis, chronic pain and poor cosmesis contributing to long-term psychological and physical morbidity. Therapeutic mammoplasty offers an alternative management strategy to both enhance the role of breast-conserving surgery and provide better outcomes. A retrospective note review was undertaken of all patients undergoing therapeutic mammoplasty for breast malignancy between 2007 and 2011. All cases were performed using a Wise pattern-reduction technique. Histology and pathological outcomes were assessed. Postoperative outcomes reviewed included wound infection, seroma and need for further intervention. During the study period, 20 patients underwent therapeutic mammoplasty with a mean follow-up duration of 36 months. The mean weight of the lumpectomy specimen was 330g. The average cancer size was 34mm, with a mean margin clearance of 7mm. There was one episode of wound infection and three of delayed wound healing at the T-junction. One patient required a mastectomy for involved margins. There were no recurrences at the most recent follow-up visit. Therapeutic mammoplasty offers a tailored approach to women with larger breasts and early breast cancers with good cosmetic results and oncological outcomes.

System analysis of spatial frequency domain imaging for quantitative mapping of surgically resected breast tissues

The feasibility of spatial frequency domain imaging (SFDI) for breast surgical margin assessment was evaluated in tissue-simulating phantoms and in fully intact lumpectomy specimens at the time of surgery. Phantom data was evaluated according to contrast-detail resolution, quantitative accuracy and model-data goodness of fit, where optical parameters were estimated by minimizing the residual sum of squares between the measured modulation amplitude and its solutions, modeled according to diffusion and scaled-Monte Carlo simulations. In contrast-detail phantoms, a 1.25-mm-diameter surface inclusion was detectable for scattering contrast >28%; a fraction of this scattering contrast (7%) was detectable for a 10 mm surface inclusion and at least 33% scattering contrast was detected up to 1.5 mm below the phantom surface, a probing depth relevant to breast surgical margin assessment. Recovered hemoglobin concentrations were insensitive to changes in scattering, except for overestimation at visible wavelengths for total hemoglobin concentrations <15 μM. The scattering amplitude increased linearly with scattering concentration, but the scattering slope depended on both the particle size and number density. Goodness of fit was comparable for the diffusion and scaled-Monte Carlo models of transport in spatially modulated, near-infrared reflectance acquired from 47 lumpectomy tissues, but recovered absorption parameters varied more linearly with expected hemoglobin concentration in liquid phantoms for the scaled-Monte Carlo forward model. SFDI could potentially reduce the high secondary excision rate associated with breast conserving surgery; its clinical translation further requires reduced image reconstruction time and smart inking strategies.

Intraoperative Imprint Evaluation of Surgical Margins in Oral Squamous Cell Carcinoma

Background: Oral squamous cell carcinoma (OSCC) is a multifactorial malignant epithelial neoplasm. Tumor clearance at the surgical margins in OSCC is a critical factor which strongly influences both the local recurrence and overall survival rate. A quick and accurate intraoperative diagnostic procedure can make a significant difference to the survival rate. Touch imprint cytology (TIC) has commonly been used in the past for the diagnosis of tumors and the detection of sentinel lymph node metastasis. It is routinely applied for intraoperative margin analysis of breast lumpectomy specimens, where it has been proven to have a good success rate. The effectiveness and reliability of TIC in the intraoperative margin evaluation of OSCC, however, has not been established so far. Objective: To investigate the diagnostic accuracy of the intraoperative TIC technique for assessing surgical margins in OSCC in comparison to paraffin-embedded hematoxylin and eosin-stained sections. Materials and Methods: Thirty previously untreated, biopsy-proven OSCC patients undergoing surgical treatment between December 2008 and September 2010 were included. Patients diagnosed with histological variants of squamous cell carcinoma (SCC) or recurrent tumor were excluded. Three hundred forty-eight touch imprint slides were prepared from 174 margins of 30 resected tumor specimens. Imprints from tumor proper were taken as positive controls. The slides were reported as positive, negative or suspicious for tumor. After all cytological interpretation was completed, the results were compared with the corresponding histological diagnosis. Results: This pioneer study showed that TIC has an overall accuracy of 83%, sensitivity of 91.1%, specificity of 74.4%, positive predictive value of 79.2% and a negative predictive value of 88.6%. The false-positive margins evaluated by TIC were 43 (12.3%) and the false-negative ones were 16 (4.6%). Conclusion: TIC is a quick, simple, inexpensive, highly accurate and reliable intraoperative technique to assess surgical margins in SCC of the oral cavity.

The Effect of Simultaneous Peripheral Excision in Breast Conservation upon Margin Status

Background Negative margins in breast conservation therapy (BCT) decrease local recurrence risk. Excision may be performed via two techniques: either as a single lumpectomy specimen or as a central segment with simultaneously resected peripheral segments (PSs). There is little data directly comparing these methods for their effect on margin status.

Comparing post‐operative human breast specimen radiograph and MRI in lesion margin and volume assessment

The purpose of this research is to evaluate the potential for identifying malignant breast lesions and their margins on large specimen MRI, in comparison to specimen radiography and clinical dynamic contrast enhanced MRI (DCE‐MRI). Breast specimens were imaged with an MR scanner immediately after surgery, with an IRB‐approved protocol and with the patients' informed consent. Specimen sizes were at least 5 cm in diameter and approximately 1 to 4 cm thick. Coronal and axial gradient echo MR images without fat suppression were acquired over the whole specimens using a 9.4T animal scanner. Findings on specimen MRI were compared with findings on specimen radiograph, and their volumes were compared with measurements obtained from clinical DCE‐MRI. The results showed that invasive ductal carcinoma (IDC) lesions were easily identified using MRI and the margins were clearly distinguishable from nearby tissue. However, ductal carcinoma in situ (DCIS) lesions were not clearly discernible and were diffused with poorly defined margins on MRI. Calcifications associated with DCIS were visualized in all specimens on specimen radiograph. There is a strong correlation between the maximum diameter of lesions as measured by radiograph and MRI (r=0.93), as well as the maximum diameter measured by pathology and radiograph/MRI (r < 0.75). The volumes of IDC measured on specimen MRI were slightly smaller than those measured on DCE‐MRI. Imaging of excised human breast lumpectomy specimens with high magnetic field MRI provides promising results for improvements in lesion identification and margin localization for IDC. However, there are technical challenges in visualization of DCIS lesions. Improvements in specimen imaging are important, as they will provide additional information to standard radiographic analysis.PACS numbers: 87.61.Tg; 87.59.B

Should Intraoperative Frozen Section Evaluation of Breast Lumpectomy Margins Become Routine Practice?

operative frozen section examination of breast lumpectomy margins was associated with a substantial reduction in the rate of reexcision. In their retrospective study, at some time after the initial lumpectomy a reexcision was performed in 48.9% of patients who did not have frozen section margin evaluation compared with only 14.9% of those in whom frozen section evaluation of the margins was performed. Further, these investigators developed a technique to overcome the methodological difficulties of attempting to cut frozen sections of fatty tissue such as margins of breast specimens. So if it is now technically feasible to obtain adequate frozen sections from lumpectomy margins and if intraoperative frozen section evaluations of these margins can reduce the need for a subsequent reexcision by almost 70%, should pathologists the world over be gearing up to routinely freeze margins of breast lumpectomy specimens? To answer this question, we must first review some fundamental data on lumpectomy margins and their association with local recurrence, and put these data into current clinical context. Various patient factors, treatment factors, and pathologic factors have been reported to be associated with an increased risk of recurrence in the ipsilateral breast (local recurrence) after breast-conserving treatment for invasive breast cancer and ductal carcinoma in situ (DCIS). Arguably the most important of these is the status of the microscopic margins of excision of the resected breast specimen. Positive margins (ie, invasive carcinoma or DCIS at an inked tissue edge) have consistently been associated with a higher risk of local recurrence than negative margins. 2

Reduced re-excisions while conserving tissue volume resected in DCIS patients.

144 Background: The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with ductal carcinoma in situ (DCIS). Many techniques have been reported to lower the positive margin rate, at a cost of additional tissue resected. A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real time, intraoperative detection of cancerous tissues at the margins of excised specimens. An analysis was performed to determine the impact on tissue volume of the previously reported improvement in candidates for re-excision associated with device use for patients with a DCIS component. Methods: 596 patients undergoing breast conservation using wire localization were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard of care lumpectomy, including palpation and any indicated additional resections. Positive readings required additional resections of the cavity; device was used on main lumpectomy specimen only. Pathologists were blinded to study arm. Tissue volume of all specimens and resections was recorded. Since reducing candidates for re-excision requires removing additional tissue associated with cancer, we looked at total tissue volume removed across all surgeries, to assess the final impact to the patient. Results: Total tissue volumes removed during all surgeries (lumpectomy and re-excisions) for patients with DCIS alone was similar between the study group and control group, while the decrease in candidates for re-excision was significant (13% vs. 37%, p=0.004). For patients with DCIS and invasive carcinoma, the total volume excised was also similar, and the decrease in re-excision candidates was significant (13% vs. 33%, p&lt;0.001). Conclusions: Unlike other techniques for reducing re-excisions, device use does not require an increase in tissue volume to achieve a significant reduction in the number of candidates for re-excision. [Table: see text]

Triple negative breast cancer is associated with an increased risk of residual invasive carcinoma after lumpectomy

To assess the potential mechanisms that may underlie increased local failure in triple negative (TN) breast cancers, an analysis was performed of the risk of residual carcinoma after lumpectomy with correlation to pathologic factors, including molecular phenotype. A review of pathologic specimens was performed for women with invasive breast cancer treated with lumpectomy followed by reexcision. Data were collected on age; tumor size, grade, and nodal stage; estrogen receptor, progesterone receptor, and human endothelial growth factor receptor 2 (Her2); extensive intraductal component; lymphovascular invasion; margins; and reexcision findings. Univariate and multivariate logistic regression analyses were performed to evaluate for associations between pathologic features of the lumpectomy specimen and reexcision findings. Molecular phenotypes were defined by conventionally used immunohistochemical pattern. Data were collected on 369 patients with breast cancer. The median age was 57 years, median tumor size was 1.5 cm, 36% had positive margins, 32% had positive lymph nodes, 73.5% had the luminal A subtype, 9.5% had the luminal B subtype, 4.5% were Her2-enriched, and 12.5% were TN. Overall, 32% of patients had invasive cancer in their reexcision specimens, and 51% of those with the TN subtype had residual invasive disease on reexcision compared with 30% to 31% for other subtypes. On univariate analysis, age, tumor size, margin status, lymphovascular invasion, nodal status, and TN subtype were associated with elevated risk of residual invasive cancer. On multivariate analysis using a forward stepwise model, TN subtype maintained significance, with an odds ratio of 3.28 (P = .002). TN subtype has a statistically significant association with an increased risk of residual tumor. This suggests the putative increase in the risk of local failure in TN patients may be related to increased residual tumor burden.

Multimodal optical imaging for detecting breast cancer

The goal of the study was to evaluate wide-field and high-resolution multimodal optical imaging, including polarization, reflectance, and fluorescence for the intraoperative detection of breast cancer. Lumpectomy specimens were stained with 0.05 mg/ml aqueous solution of methylene blue (MB) and imaged. Wide-field reflectance images were acquired between 390 and 750 nm. Wide-field fluorescence images were excited at 640 nm and registered between 660 and 750 nm. High resolution confocal reflectance and fluorescence images were excited at 642 nm. Confocal fluorescence images were acquired between 670 nm and 710 nm. After imaging, the specimens were processed for hematoxylin and eosin (H&E) histopathology. Histological slides were compared with wide-field and high-resolution optical images to evaluate correlation of tumor boundaries and cellular morphology, respectively. Fluorescence polarization imaging identified the location, size, and shape of the tumor in all the cases investigated. Averaged fluorescence polarization values of tumor were higher as compared to normal tissue. Statistical analysis confirmed the significance of these differences. Fluorescence confocal imaging enabled cellular-level resolution. Evaluation and statistical analysis of MB fluorescence polarization values registered from single tumor and normal cells demonstrated higher fluorescence polarization from cancer. Wide-field high-resolution fluorescence and fluorescence polarization imaging shows promise for intraoperative delineation of breast cancers.

3D Pathology Volumetric Technique: A Method for Calculating Breast Tumour Volume from Whole-Mount Serial Section Images

Tumour size, most commonly measured by maximum linear extent, remains a strong predictor of survival in breast cancer. Tumour volume, proportional to the number of tumour cells, may be a more accurate surrogate for size. We describe a novel “3D pathology volumetric technique” for lumpectomies and compare it with 2D measurements. Volume renderings and total tumour volume are computed from digitized whole-mount serial sections using custom software tools. Results are presented for two lumpectomy specimens selected for tumour features which may challenge accurate measurement of tumour burden with conventional, sampling-based pathology: (1) an infiltrative pattern admixed with normal breast elements; (2) a localized invasive mass separated from the in situ component by benign tissue. Spatial relationships between key features (tumour foci, close or involved margins) are clearly visualized in volume renderings. Invasive tumour burden can be underestimated using conventional pathology, compared to the volumetric technique (infiltrative pattern: 30% underestimation; localized mass: 3% underestimation for invasive tumour, 44% for in situ component). Tumour volume approximated from 2D measurements (i.e., maximum linear extent), assuming elliptical geometry, was seen to overestimate volume compared to the 3D volumetric calculation (by a factor of 7x for the infiltrative pattern; 1.5x for the localized invasive mass).

Filariasis of breast: An unusual presentation

Lymphatic filariasis involving the female breast is unusual but not rare, especially where filariasis is endemic. In this report, we present a 38-year-old married woman presenting with a painless mass in the left breast of 4 months duration and slightly painful masses in both axillae for similar duration. Examination revealed a small, discrete, firm, non-tender mass in lower inner quadrant of left breast with associated bilateral, tender axillary lymphadenopathy. Mammography suggested a well-defined mass lesion in the left breast without any architectural distortion or micro calcifications. Ultrasonography (USG) of the breast suggested hypoechoic lesion in infero-medial quadrant of left breast and bilateral axillary lymphadenopathy. USG-guided fine needle aspiration cytology (FNAC) from the breast lump showed non-specific findings like eosinophilic infiltrate and occasional granuloma, while that from the enlarged lymph nodes in the axilla revealed inflammatory cells, giant cells, and epithelioid cells. Histopathological examination of the lumpectomy specimen revealed adult microfilaria with characteristic morphology of Wuchereria bancrofti.

PD02-04: A Randomized, Prospective, Multicenter Study of the Impact of Intraoperative Margin Assessment with Adjunctive Use of MarginProbe vs. Standard of Care.

Abstract Background: The current practice of breast conserving surgery (BCS) involves intraoperative margin assessment according to the surgeon's gross assessment and judgment. The failure of this intraoperative assessment has been associated with a 20–30% reoperation rate to assure negative margins. MarginProbe (Dune Medical Devices) was developed to provide real-time assessment of lumpectomy specimens to evaluate for the presence of disease at the surgical margins. A 21-center international pivotal study was conducted to determine if adjunctive use of MarginProbe can enable surgeons to identify positive margins intraoperatively, resulting in fewer patients who are candidates for re-excision procedures. Methods: 664 women with non-palpable lesions undergoing lumpectomy for DCIS and invasive cancer were enrolled and 596 randomized (1:1) in the operating room following standard of care (SOC) lumpectomy. In the device arm, MarginProbe was used to assess all surfaces of the lumpectomy specimen and positive readings required additional resections. All specimens were inked in the operating room by the surgeon. All specimens were examined to verify excision of the target lesion intraoperatively. Pathologists were blinded to study arm. Additional surgeries to re-excise involved margins were performed per each individual site criteria. Patients were followed for 2 months following surgery; additional procedures were documented. Safety was assessed by reports of adverse events. Results: No safety concerns were raised. Of the 298 patients in each arm, 55% (163/298) patients in the device arm (D) and 49% (147/298) in the control arm (C) had at least one positive margin on the main lumpectomy specimen (≤ 1mm). Surgeons’ ability to identify and resect all positive margins per patient was significantly improved with device use (D: 72% (117/163), C: 22% (33/147); p &amp;lt; 0.0001). Following lumpectomy, the number of patients having positive margins due to failed intraoperative assessment (excluding skin or fascia) was reduced by 57% in the device arm (D: 42/298(14%), C: 98/298(32.8%), p&amp;lt;0.0001), leading to a 50% reduction in re-excisions for this group (D: 31/298 (10.4%), C: 62/298 (20.8%); p=0.001). There was no significant difference in tissue volume removed (D: 93cc, C: 85cc; 25cc non-inferiority delta, p &amp;lt;0.0001). Normalized to baseline breast size, tissue volume in the device arm was non-inferior to the control arm (D: 15.1%, C: 12.5%, 5% non-inferiority delta, p &amp;lt;0.0001). For patients having at least one positive margin prior to intraoperative assessment, there was a trend in the device arm towards smaller average tissue volume resected to achieve clear margins (D: 99cc, C: 108cc; p=0.6). Conclusions: Adjunctive use of MarginProbe during BCS significantly improved surgical outcomes by improving surgeons’ ability to identify and immediately resect positive margins, reducing the number of patients requiring re-excision. Overall tissue volume removed was not statistically different in the two arms. Patients in the device arm who had positive margins prior to intraoperative assessment had less average tissue volume removed and required fewer re-excisions to achieve appropriate margins. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD02-04.

P3-12-02: Intra-Operative Margin Assessment of Diffuse Disease with MarginProbe” as an Adjunct to Standard of Care, Results from a Randomized Prospective Multi Center Study.

Abstract Background The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with diffuse disease such as DCIS and lobular pathology. A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real time, intraoperative detection of cancerous tissues at the margins of excised specimens. A study was performed to determine if there was a device-associated improvement in complete surgical resection (CSR) and therefore a decrease in the rate of patients requiring re-excision with these disease types. The current analysis stratified the data based on tumor type with a special focus on DCIS patients, patient with a DCIS component, and lobular patients. Methods: All 596 patients underwent breast conservation, with image-guided localization, and were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard lumpectomy procedure, including palpation followed by additional cavity resections as indicated. In the device arm, MarginProbe was used on each specimen margin and device positive readings required additional resections of the cavity. Pathologists were blinded to study arm. Re-excision criteria were not dictated by the protocol. A primary endpoint of this study was CSR, defined as the correct intraoperative identification and resection (if not skin or fascia) of all positive margins on the main lumpectomy specimen. Positive lumpectomy specimens were defined as those having at least one margin having cancer ≤1mm from the surface. Successful CSR results in reduced positive margin rate after lumpectomy. Results: Results are presented in Table 1. The improvement in CSR was significant for all diagnosis types. The decrease in candidates for re-excision due to failed CSR was significant for all DCIS and mixed tumor types. Conclusions: Use of the device resulted in significant improvement in CSR and therefore a significant decrease in the need for reexcisions. Further studies should be conducted to evaluate the use of the device for additional patient cohorts, such as patients receiving neoadjuvant treatment and patients who have undergone prior breast surgery. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-02.

Study of Fine Needle Aspiration Cytology of Breast Lump: Correlation of Cytologically Malignant Cases with their Histological Findings

Background: In Bangladesh a large number of patients have been suffering from breast cancer and with each passing year, the number is increasing. Objectives: To correlate breast lesions diagnosed as cytologically malignant with their histological findings. Methods: This is a prospective study carried out in the Department of Pathology, BSMMU, Dhaka during the period of January 2009 to December 2009. Patients with breast lump, having malignant breast lesions on cytology were included in the study. A total of 524 patients with breast lump underwent FNA examination for the diagnosis during this period. FNA slides were examined under light microscope after Papanicolaou staining and were categorized into five groups: i) inadequate ii) benign iii) atypical cells iv) suspicious for malignancy and v) malignant. Of these, 431 were diagnosed as benign, 4 as atypical, 17 were diagnosed as suspicious for malignancy and 72 cases were diagnosed as malignant. Out of these 72 cases, which were cytologically diagnosed as malignant, 55 corresponding surgical specimens (either mastectomy or lumpectomy specimens) were received for histopathology. The sections were stained with haematoxylin and eosin for microscopic examination. Results: 55 cases which were diagnosed as malignant by FNAC were found to be malignant by histopathology. 54 (98.18%) were invasive ductal carcinoma (NOS) and one (1.82%) was mucinous carcinoma. In this study, considering only cases with a definitive diagnosis of malignancy, the sensitivity of FNAC to diagnose the disease was 100% and accuracy was 100% and Chi-square test revealed Chi-square value 10.83 (P< 0.001). Conclusion: From the present study it is evident that FNAC is a simple and reliable method. No local anaesthesia is required. Operative risk of surgical biopsy, danger of post operative infection can be avoided by adopting the procedure. It helps to confirm the clinical impression without open biopsy. Key words: Breast lump; FNAC; Mastectomy; Malignancy. DOI: http://dx.doi.org/10.3329/bsmmuj.v4i2.8631 BSMMU J 2011; 4(2):60-64

Use of a novel device to reduce positive margins for ductal carcinoma in situ.

87 Background: The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with ductal carcinoma in situ (DCIS). A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real-time, intraoperative detection of cancerous tissues at the margins of excised specimens. A study was performed to determine if there was a device-associated improvement in complete surgical resection (CSR) and therefore a decreased re-excision rate in patients with a DCIS component. Methods: 596 patients who were undergoing breast conservation using needle localization were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard of care lumpectomy, including palpation followed by indicated additional cavity resections. Device positive readings required additional resections of the cavity. Pathologists were blinded to study arm. A primary endpoint of this study was CSR, defined as the correct intraoperative identification and resection (if not skin or fascia) of all positive margins on the main lumpectomy specimen. Positive lumpectomy specimens were those having at least one margin having cancer ≤1mm from the surface. Successful CSR results in reduced positive margin rate after lumpectomy. Results: The improvement in CSR was significant for each diagnosis (p&lt;0.0001). The decrease in candidates for reexcision due to failed CSR was significant for all pathology involving DCIS (p&lt;0.0001). Overall results are presented in the table. Conclusions: Device use delivered significant improvement in CSR and therefore a significant decrease in reexcision rates for patients with DCIS. Further studies need to be conducted evaluating the use of the device on additional margins that the surgeon may resect or in the actual cavity. [Table: see text]

Cavity margins examination in breast-conserving therapy

There is a good consensus that the pathologic lumpectomy margin status is the most important factor to determine the risk of local recurrence of carcinoma after breast-conserving therapy. However, there is no consensus regarding the definition of a complete excision or an adequate margin and the reported rates of repeat surgery for positive margins range from 10 to 57%. Therefore, an alternative technique of margin evaluation, called cavity shaving or cavity margin shaving has been proposed and applied by some surgical teams in order to reduce the need for re-excisions and to detect multifocality. We aim to describe in this review how to handle, analyse and report breast lumpectomy specimens with associated cavity margins and to discuss the potential advantages and drawbacks of this method.