Role for Intraoperative Margin Assessment in Patients Undergoing Breast-Conserving Surgery

Cabıoğlu, Neslihan; Hunt, Kelly K.; Şahin, Ayşegül; Kuerer, Henry Mark; Babiera, Gildy; Singletary, S. Eva; Whitman, Gary J.; Ross, Merrick I.; Ames, Frederick C.; Feig, Barry W.; Buchholz, Thomas A.; Meric‐Bernstam, Funda

doi:10.1245/s10434-006-9236-0

Cited by 234 publications

(164 citation statements)

References 43 publications

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“…Patients with DCIS (possibly the most prevalent precursor to invasive breast cancer [6][7][8][9][10][11]) currently undergo some combination of breast conserving surgery, radiation therapy, and hormonal therapy. Breast conserving surgery fails to remove the entire tumor 38-72% of the time, requiring up to three surgeries for adequate tumor excision [12][13][14]. In the absence of adjuvant radiation and hormonal therapy, the estimated rate of recurrence after surgery is up to 25%.…”

Section: Introductionmentioning

confidence: 99%

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

Edgerton

Chuang

Macklin

et al. 2011

Analytical Cellular Pathology

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Abstract. We introduce a novel "mathematical pathology" approach, founded on a biophysical model, to identify robust patientspecific predictors of tumor growth useful in clinical practice to improve the accuracy of diagnosis/prognosis and intervention. In accordance with biological observations, our model simulates the diffusion-limited in-situ tumors with a relatively short phase of fast initial growth, followed by a prolonged slow-growth phase where tumor size is constrained primarily by the relative weight of cell mitosis and death. The former phase may only last for a few months, so that at the time of diagnosis, we may assume that most tumors will have entered the phase where their size is changing slowly. Based on this prediction, we hypothesize that the volume of breast with ducts affected by in-situ tumors at the time of diagnosis will be closely approximated by a modelderived mathematical function based on the ratio of tumor cell proliferation-to-apoptosis indices and on the extent of diffusion of cell nutrients (diffusion penetration length), which can be measured from immunohistochemical and morphometric analysis of patient histopathology specimens without the need for multiple-time measurements. We tested this idea in a retrospective study of 17 patients by staining breast tumor specimens containing ductal carcinoma in situ for mitosis with Ki-67 and for apoptosis with cleaved caspase-3 and counting cells positive for each marker. We also determined diffusion penetration by measuring the thickness of viable rims of tumor cells within ducts. Using the ensuing ratios, we applied the model to determine a predicted surgical volume or tumor size. We then corroborated our hypothesis by comparing the predicted size of each tumor based on our model with the actual size of the pathological specimen after tumor excision (R 2 = 0.74-0.88). In addition, for the 17 cases studied, both histological grade and mammography were not found to correlate with tumor size (R 2 = 0.08-0.47). We conclude that our mathematical pathology approach yields a high degree of accuracy in predicting the size of tumors based on the mitotic/apoptotic index and on diffusion penetration. By obtaining these ratios at the time of initial biopsy, pathologists can employ our model to predict the size of the tumor and thereby inform surgeons how much tissue to remove (surgical volume). We discuss how results from the model have implications concerning the current debate on recommendations for screening mammography, while the model itself may contribute to better planning of breast conservation surgery.

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Section: Introductionmentioning

confidence: 99%

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

Edgerton

Chuang

Macklin

et al. 2011

Analytical Cellular Pathology

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“…While a lumpectomy has clear advantages over mastectomy, one disadvantage is the need sometimes to return to the operating room for a re-excision lumpectomy. Re-excision rates are high, ranging from 20% to 70% in the literature, and in addition to the inconvenience and added costs, re-excision lumpectomies may result in added complications and diminish the aesthetic outcome [2][3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Residual disease after re‐excision lumpectomy for close margins

Sabel

Rogers

Griffith

et al. 2008

Journal of Surgical Oncology

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Introduction: While a positive margin after an attempt at breast conservation therapy (BCT) is a reason for concern, there is more controversy regarding close margins. When re-excisions are performed, there is often no residual disease in the new specimen, calling into question the need for the procedure. We sought to examine the incidence of residual disease after re-excision for close margins and to identify predictive factors that may better select patients for re-excision. Methods: Our IRB-approved prospective breast cancer database was queried for all breast cancer patients who underwent a re-excision lumpectomy for either close or positive margins after an attempt at BCT. Close margins are defined as 2 mm for invasive carcinoma and 3 mm for DCIS. Clinicopathologic features were correlated with the presence of residual disease in the re-excision specimen. Results: Three hundred three patients (32%) underwent re-operation for either close (173) or positive (130) margins. Overall, 33% had residual disease identified, 42% of DCIS patients and 29% of patients with invasive disease, nearly identical to patients with positive margins. For patients with DCIS, only younger age was significantly related to residual disease. For patients with invasive cancer, only multifocality was significantly associated with residual disease ). However, patients without multifocality still had a substantial risk of residual disease. Discussion: The presence of residual disease appears equal between re-excisions for close and positive margins. No subset of patients with either DCIS or invasive cancer could be identified with a substantially lower risk of residual disease.

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“…However, ensuring the complete excision of the tumor remains one of the key challenges in tissue-conserving surgery. Failure to remove all tumor cells increases the risk of tumor recurrence and the need for secondary surgery (6,7).…”

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confidence: 99%

Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy

Kong

Rowlands

Varma

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

225

223

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Tissue-conserving surgery is used increasingly in cancer treatment. However, one of the main challenges in this type of surgery is the detection of tumor margins. Histopathology based on tissue sectioning and staining has been the gold standard for cancer diagnosis for more than a century. However, its use during tissue-conserving surgery is limited by time-consuming tissue preparation steps (1-2 h) and the diagnostic variability inherent in subjective image interpretation. Here, we demonstrate an integrated optical technique based on tissue autofluorescence imaging (high sensitivity and high speed but low specificity) and Raman scattering (high sensitivity and high specificity but low speed) that can overcome these limitations. Automated segmentation of autofluorescence images was used to select and prioritize the sampling points for Raman spectroscopy, which then was used to establish the diagnosis based on a spectral classification model (100% sensitivity, 92% specificity per spectrum). This automated sampling strategy allowed objective diagnosis of basal cell carcinoma in skin tissue samples excised during Mohs micrographic surgery faster than frozen section histopathology, and one or two orders of magnitude faster than previous techniques based on infrared or Raman microscopy. We also show that this technique can diagnose the presence or absence of tumors in unsectioned tissue layers, thus eliminating the need for tissue sectioning. This study demonstrates the potential of this technique to provide a rapid and objective intraoperative method to spare healthy tissue and reduce unnecessary surgery by determining whether tumor cells have been removed.

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Role for Intraoperative Margin Assessment in Patients Undergoing Breast-Conserving Surgery

Cited by 234 publications

References 43 publications

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

Residual disease after re‐excision lumpectomy for close margins

Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy

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