Suzanne B. Coopey

The Safety of Multiple Re-excisions after Lumpectomy for Breast Cancer

BackgroundBreast cancer patients may undergo multiple re-excisions after lumpectomy in an attempt to obtain clear margins and avoid mastectomy. We sought to determine the overall local recurrence rate and surgical outcome of patients undergoing two or more re-excisions and to identify predictors of success in attaining clear margins.MethodsRetrospective review of breast cancer patients who underwent lumpectomy for invasive cancer or ductal carcinoma in situ (DCIS) from 1997 to 2007. Patients who underwent two or more re-excisions were identified and analyzed.ResultsWe identified 3,737 patients who underwent lumpectomy over this 10-year period. 875 (23.4%) had close or positive margins requiring a second procedure; 797 (91.1%) had a re-excision; and 78 (8.9%) went directly to mastectomy. Seventy patients underwent multiple re-excisions; 66 patients had 2 re-excisions, 3 patients had 3 re-excisions, and 1 patient had 4 re-excisions. 70% (49/70) of multiple re-excision patients achieved clear margins (26 DCIS, 35 T1, 8 T2, and 1 T3 tumors). All 49 patients who successfully treated with multiple re-excisions received radiation. At a median follow-up of 64 months, 1 of 49 (2.0%) patients had an in-breast recurrence, and 1 of 49 (2.0%) patients had a distant recurrence. Statistically significant risk factors for persistently involved margins after two re-excisions included multifocality and positive lymph node status.ConclusionMultiple re-excisions to obtain clear margins are a safe alternative to mastectomy for women with invasive cancer or DCIS. There is an acceptably low risk of local and systemic failure when negative margins are ultimately achieved.

The feasibility of using natural language processing to extract clinical information from breast pathology reports.

Objective: The opportunity to integrate clinical decision support systems into clinical practice is limited due to the lack of structured, machine readable data in the current format of the electronic health record. Natural language processing has been designed to convert free text into machine readable data. The aim of the current study was to ascertain the feasibility of using natural language processing to extract clinical information from >76,000 breast pathology reports. Approach and Procedure: Breast pathology reports from three institutions were analyzed using natural language processing software (Clearforest, Waltham, MA) to extract information on a variety of pathologic diagnoses of interest. Data tables were created from the extracted information according to date of surgery, side of surgery, and medical record number. The variety of ways in which each diagnosis could be represented was recorded, as a means of demonstrating the complexity of machine interpretation of free text. Results: There was widespread variation in how pathologists reported common pathologic diagnoses. We report, for example, 124 ways of saying invasive ductal carcinoma and 95 ways of saying invasive lobular carcinoma. There were >4000 ways of saying invasive ductal carcinoma was not present. Natural language processor sensitivity and specificity were 99.1% and 96.5% when compared to expert human coders. Conclusion: We have demonstrated how a large body of free text medical information such as seen in breast pathology reports, can be converted to a machine readable format using natural language processing, and described the inherent complexities of the task.

Positive Nipple Margins in Nipple-Sparing Mastectomies: Rates, Management, and Oncologic Safety

BACKGROUND When a nipple margin of a nipple-sparing mastectomy (NSM) contains malignancy, current practice includes removal of the nipple or nipple areola complex (NAC). We evaluated rates and trends of positive nipple margins, subsequent management, and oncologic outcomes. STUDY DESIGN A retrospective chart review of all NSM at our institution from 2007 to 2014 was performed. A descriptive analysis was performed of patients with positive nipple/subareolar margins. RESULTS Among 1,326 NSM, 43 of 642 (6.7%) therapeutic and 3 of 684 (0.4%) prophylactic NSM had positive nipple margins. Nipple or NAC excision was performed for 39 of 46 (85%) positive nipple margins: 20 of 39 (51%) had nipple only and 19 of 39 (49%) had the entire NAC excised. Practice evolved to remove only the nipple and retain the areola for positive nipple margins: in 2007 to 2011, 7 of 17 (41%) underwent nipple-only excision compared with 14 of 22 (64%) in 2012 to 2014. Among 39 excised nipples/NAC, 28 (72%) contained no residual malignancy, while 8 contained ductal carcinoma in situ (DCIS), 2 had invasive lobular carcinoma, and 1 had invasive ductal carcinoma. With experience, rates of positive nipple margins for therapeutic NSM decreased from 11% (17 of 160) in 2007 to 2011 to 5.4% (26 of 482) in 2012 to 2014 (p < 0.05). At 36 month median follow-up, there were no recurrences in the nipple/NAC. CONCLUSIONS Early results suggest that excision of the nipple with retention of the areola is a safe approach for management of a positive nipple margin after NSM. With experience, low rates of positive nipple margins are possible in therapeutic NSM. Overall risk of nipple/NAC recurrence after NSM remains extremely low.

A pilot study evaluating shaved cavity margins with micro-computed tomography: a novel method for predicting lumpectomy margin status intraoperatively.

Microscopically clear lumpectomy margins are essential in breast conservation, as involved margins increase local recurrence. Currently, 18–50% of lumpectomies have close or positive margins that require re‐excision. We assessed the ability of micro‐computed tomography (micro‐CT) to evaluate lumpectomy shaved cavity margins (SCM) intraoperatively to determine if this technology could rapidly identify margin involvement by tumor and reduce re‐excision rates. Twenty‐five SCM from six lumpectomies were evaluated with a Skyscan 1173 table top micro‐CT scanner (Skyscan, Belgium). Micro‐CT results were compared to histopathological results. We scanned three SCM at once with a 7‐minute scanning protocol, and studied a total of 25 SCM from six lumpectomies. Images of the SCM were evaluated for radiographic signs of breast cancer including clustered microcalcifications and spiculated masses. SCM were negative by micro‐CT in 19/25 (76%) and negative (≥2 mm) by histopathology in 19/25 (76%). Margin status by micro‐CT was concordant with histopathology in 23/25 (92%). Micro‐CT overestimated margin involvement in 1/25 and underestimated margin involvement in 1/25. Micro‐CT had an 83.3% positive predictive value, a 94.7% negative predictive value, 83.3% sensitivity, and 94.7% specificity for evaluation of SCM. Evaluation of SCM by micro‐CT is an accurate and promising method of intraoperative margin assessment in breast cancer patients. The scanning time required is short enough to permit real‐time feedback to the operating surgeon, allowing immediate directed re‐excision.

Management of Positive Sub-areolar/Nipple Duct Margins in Nipple-Sparing Mastectomies

We evaluated management of positive sub‐areolar/nipple duct margins in nipple‐sparing mastectomies (NSM) at our institution. Retrospective chart review of all NSM from January 2007 to April 2012 was performed and patient, tumor, and treatment information was collected. Sub‐areolar/nipple duct margins included ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub‐areolar/nipple duct margins; 21 of 220 cancer‐bearing breasts (10%) and 1 of 218 prophylactic mastectomies (0.5%). Positive margins included four with invasive lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management included removal of eight nipples and nine nipple areola complexes (NAC). Four of 17 nipple/NAC specimens had evidence of residual DCIS and none had residual invasive cancer. The majority of nipple/NAC specimens excised for a positive margin had no residual malignancy. Future studies are needed to determine the extent of NAC tissue removal required for positive margins.

Oncologic Safety of Nipple-Sparing Mastectomy in Women with Breast Cancer

BACKGROUND Nipple-sparing mastectomy (NSM) has gained popularity for breast cancer treatment and prevention. There are limited data about long-term oncologic safety of this procedure. STUDY DESIGN We reviewed oncologic outcomes of consecutive therapeutic NSM at a single institution. Nipple-sparing mastectomy was offered to patients with no radiologic or clinical evidence of nipple involvement. RESULTS There were 2,182 NSM performed from 2007 to 2016. Long-term outcomes were assessed in the 311 NSM performed in 2007 to 2012 for Stages 0 to 3 breast cancer; 240 (77%) NSM were for invasive cancer and 71 (23%) were for ductal carcinoma in situ. At 51 months median follow-up, 17 patients developed a recurrence of their cancer. Estimated disease-free survival was 95.7% at 3 years and 92.3% at 5 years. There were 11 (3.7%) locoregional recurrences and 8 (2.7%) distant recurrences; 2 patients had simultaneous locoregional and distant recurrences. There were 2 breast cancer-related deaths in patients with isolated distant recurrences. No patient in the entire 2,182 NSM cohort has had a recurrence in the retained nipple-areola complex. CONCLUSIONS Rates of locoregional and distant recurrence are acceptably low after nipple-sparing mastectomy in patients with breast cancer. No patient in our series has had a recurrence involving the retained nipple areola complex.

Intraoperative micro-computed tomography (micro-CT): a novel method for determination of primary tumour dimensions in breast cancer specimens

OBJECTIVES Micro-CT is a promising modality to determine breast tumour size in three dimensions in intact lumpectomy specimens. We compared the accuracy of tumour size measurements using specimen micro-CT with measurements using multimodality pre-operative imaging. METHODS A tabletop micro-CT was used to image breast lumpectomy specimens. The largest tumour dimension on three-dimensional reconstructed micro-CT images of the specimen was compared with the measurements determined by pre-operative mammography, ultrasound and MRI. The largest dimension of pathologic invasive cancer size was used as the gold standard reference to assess the accuracy of imaging assessments. RESULTS 50 invasive breast cancer specimens in 50 patients had micro-CT imaging. 42 were invasive ductal carcinoma, 6 were invasive lobular carcinoma and 2 were other invasive cancer. Median patient age was 63 years (range 33-82 years). When compared with the largest pathologic tumour dimension, micro-CT measurements had the best correlation coefficient (r = 0.82, p < 0.001) followed by MRI (r = 0.78, p < 0.001), ultrasound (r = 0.61, p < 0.001) and mammography (r = 0.40, p < 0.01). When compared with pre-operative modalities, micro-CT had the best correlation coefficient (r = 0.86, p < 0.001) with MRI, followed by ultrasound (r = 0.60, p < 0.001) and mammography (r = 0.54, p < 0.001). Overall, mammography and ultrasound tended to underestimate the largest tumour dimension, while MRI and micro-CT overestimated the largest tumour dimension more frequently. CONCLUSION Micro-CT is a potentially useful tool for accurate assessment of tumour dimensions within a lumpectomy specimen. Future studies need to be carried out to see if this technology could have a role in margin assessment. ADVANCES IN KNOWLEDGE Micro-CT is a promising new technique which could potentially be used for rapid assessment of breast cancer dimensions in an intact lumpectomy specimen in order to guide surgical excision.

Using machine learning to parse breast pathology reports

Purpose Extracting information from electronic medical record is a time-consuming and expensive process when done manually. Rule-based and machine learning techniques are two approaches to solving this problem. In this study, we trained a machine learning model on pathology reports to extract pertinent tumor characteristics, which enabled us to create a large database of attribute searchable pathology reports. This database can be used to identify cohorts of patients with characteristics of interest.Methods We collected a total of 91,505 breast pathology reports from three Partners hospitals: Massachusetts General Hospital, Brigham and Women’s Hospital, and Newton-Wellesley Hospital, covering the period from 1978 to 2016. We trained our system with annotations from two datasets, consisting of 6295 and 10,841 manually annotated reports. The system extracts 20 separate categories of information, including atypia types and various tumor characteristics such as receptors. We also report a learning curve analysis to show how much annotation our model needs to perform reasonably.Results The model accuracy was tested on 500 reports that did not overlap with the training set. The model achieved accuracy of 90% for correctly parsing all carcinoma and atypia categories for a given patient. The average accuracy for individual categories was 97%. Using this classifier, we created a database of 91,505 parsed pathology reports.ConclusionsOur learning curve analysis shows that the model can achieve reasonable results even when trained on a few annotations. We developed a user-friendly interface to the database that allows physicians to easily identify patients with target characteristics and export the matching cohort. This model has the potential to reduce the effort required for analyzing large amounts of data from medical records, and to minimize the cost and time required to glean scientific insight from these data.

The Nipple is Just Another Margin

The indications for nipple-sparing mastectomy (NSM), also termed ‘‘total skin-sparing mastectomy,’’ have evolved to include the majority of patients undergoing mastectomy. Few absolute contraindications to nipple sparing remain. These have included direct involvement of the nipple– areola complex (NAC), observed on preoperative clinical exam or imaging, or involvement of the nipple margin tissue seen on pathology. At some centers, patients with locally advanced breast cancer are considered eligible for nipple sparing after neoadjuvant systemic therapy and with postmastectomy radiation. Cosmetic contraindications to nipple sparing include factors that would result in an unacceptable posi

Breast Cancer Risk and Follow-up Recommendations for Young Women Diagnosed with Atypical Hyperplasia and Lobular Carcinoma In Situ (LCIS).

BackgroundThe risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population.MethodsA retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed. Patient characteristics, pathology and follow-up were determined from chart review.ResultsWe identified 58 young women with atypical breast lesions. Median age at diagnosis was 31 years (range 19–34). 34 patients had ADH, 11 had ALH, 8 had LCIS, and 5 had severe ADH.7 (12%) patients developed breast cancer. The median follow-up was 86 months (range 1–298). Median time to cancer diagnosis was 90 months (range 37–231). 4 cancers were on the same side, 3 were contralateral. 4 were IDC, 1 was ILC, and 2 were DCIS.Cancer was detected by screening mammogram in 4 patients, 2 by clinical exam, and 1 unknown. In the entire cohort, 26 (45%) patients had screening mammograms as part of their follow up, 12 patients had only clinical follow up, and 20 had no additional follow up. 13 patients required subsequent biopsies.ConclusionYoung women with atypical breast lesions are at a markedly increased risk for developing breast cancer and should be followed closely. Based on our findings, we recommend close clinical follow-up, MRI starting at age 25 through age 29, and screening mammograms for those over 30 in this high-risk group of patients.