Positive Nipple Margins in Nipple-Sparing Mastectomy: Management of Nipples Containing Cancer or Atypia.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe approach for breast cancer treatment and prevention; however, there are little long-term data to guide management for patients whose nipple margins contain tumor or atypia. METHODS: NSM patients with tumor or atypia in their nipple margin were identified from a prospectively maintained, single-institution database of consecutive NSMs. Patient and tumor characteristics, treatment, recurrence, and survival data were assessed. RESULTS: A total of 3158 NSMs were performed from June 2007 to August 2019. Nipple margins contained tumor in 117 (3.7%) NSMs and atypia only in 164 (5.2%) NSMs. Among 117 nipple margins that contained tumor, 34 (29%) margins contained invasive cancer, 80 (68%) contained ductal carcinoma in situ only, and 3 (3%) contained lymphatic vessel invasion only. Management included nipple-only excision in 67 (57%) breasts, nipple-areola complex excision in 35 (30%) breasts, and no excision in 15 (13%) breasts. Only 23 (24%) excised nipples contained residual tumor. At 67 months median follow-up, there were 2 (1.8%) recurrences in areolar or peri-areolar skin, both in patients with nipple-only excision. Among 164 nipple margins containing only atypia, 154 (94%) nipples were retained. At 60 months median follow-up, no patient with atypia alone had a nipple or areola recurrence. CONCLUSIONS: Nipple excision is effective management for nipple margins containing tumor. No intervention is required for nipple margins containing only atypia. Our results support broad eligibility for NSM with careful nipple margin assessment.

Oncologic Safety of Nipple-Sparing Mastectomy for Breast Cancer in BRCA Gene Mutation Carriers: Outcomes at 70 Months Median Follow-Up.

BACKGROUND: Retention of the nipple-areola complex with nipple-sparing mastectomy (NSM) techniques provides a more natural cosmetic result than procedures that sacrifice the nipple. While the oncologic safety of NSM is established by several studies, there is little long-term data on outcomes in BRCA mutation carriers with breast cancer. PATIENTS AND METHODS: BRCA1/2 mutation carriers who underwent NSM and immediate reconstruction from 2008 to 2019 were reviewed and patients with breast cancer on biopsy or final pathology were included. Patient demographics and tumor characteristics, as well as treatment, recurrence, and survival data were collected. RESULTS: A total of 114 therapeutic NSM were performed in 105 BRCA mutation carriers (56 BRCA1, 47 BRCA2, and two women with both mutations). Median age was 45 years. Cancers were 18% stage 0, 52% stage I, 27% stage II, and 3% stage III. Mean invasive tumor size was 1.6 cm and 33 (35%) invasive tumors were triple negative. There were five (4.4%) positive nipple margins on final pathology; all underwent nipple excision. Most patients (80, 76%) received systemic therapy: 65 (62%) received chemotherapy and 48 (46%) received endocrine therapy. At 70 months median follow-up (range 15-150 months), no patient had developed a recurrence in the retained nipple-areola complex or at the site of a nipple excised for a positive margin. The rate of locoregional recurrence outside the nipple was 2.6%, and the rate of distant recurrence was 3.8%. Overall survival was 96%. CONCLUSIONS: NSM is a safe option for BRCA1 and BRCA2 mutation carriers who undergo mastectomy for breast cancer.

Nipple-Sparing Mastectomy versus Skin-Sparing Mastectomy: Does Saving the Nipple Impact Short- and Long-Term Patient Satisfaction?

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe alternative to skin-sparing mastectomy (SSM). This study evaluated whether NSM patients were more satisfied than SSM patients in short- and long-term follow-up. METHODS: Women who underwent NSM or SSM between 2009 and 2019 completed a postoperative BREAST-Q survey at least 1 year after surgery and patient characteristics were compared. Patient satisfaction at 1-5 years and 6-10 years after NSM and SSM were analyzed. RESULTS: Overall, 431 patients were included; 247 had NSM and 184 had SSM 1-10 years prior to BREAST-Q survey completion. SSM patients were older, had higher body mass index (BMI), larger breast weight, and more hypertension than NSM patients, but oncologic treatments were similar between groups. BREAST-Q Psychosocial Well-Being and Sexual Well-Being scores were significantly higher in NSM patients compared with SSM patients in the 1-5 years cohort; however, scores attenuated in the 6-10 years cohort. Satisfaction with breasts was nearly significantly higher in NSM patients compared with SSM patients in the 1-5 years cohort (p = 0.056), but no different in the 6-10 years cohort. Receipt of adjuvant chemotherapy, receipt of postmastectomy radiation therapy, and BMI ≥30 were independent risk factors for dissatisfaction with breasts. CONCLUSIONS: Women who are not candidates for NSM should be reassured that long-term qualify of life is not significantly different between SSM and NSM. Dissatisfaction with reconstructed breasts is linked with other factors (besides the nipple), which patients should be made aware of at the time of surgical decision making.

Performance of a novel protease-activated fluorescent imaging system for intraoperative detection of residual breast cancer during breast conserving surgery.

PURPOSE: Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20-40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types. METHODS: We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software. RESULTS: Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81-5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision. CONCLUSIONS: Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.

How Protective are Nipple-Sparing Prophylactic Mastectomies in BRCA1 and BRCA2 Mutation Carriers?

BACKGROUND: Nipple-sparing mastectomy (NSM) is now routinely offered to BRCA mutation carriers for risk reduction. We assessed the rates of ipsilateral cancer events after prophylactic and therapeutic NSM in BRCA1 and BRCA2 mutation carriers. METHODS: BRCA1 and BRCA2 mutation carriers undergoing NSM from October 2007 to June 2019 were identified in a single-institution prospective database, with variants of unknown significance being excluded. Patient, tumor, and outcomes data were collected. Follow-up analysis was by cumulative breast-years (total years of follow-up of each breast) and woman-years (total years of follow-up of each woman). RESULTS: Overall, 307 BRCA1 and BRCA2 mutation carriers (160 BRCA1, mean age 41.4 years [range 21-65]; and 147 BRCA2, mean age 43.8 years [range 23-65]) underwent 607 NSMs, with a median follow-up of 42 months (range 1-143). 388 bilateral prophylactic NSMs had 744 cumulative woman-years of follow-up, with no new cancers seen (< 0.0013 new cancers per woman-years); 251 BRCA1 prophylactic NSMs had 1034 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0010 per breast-year); 66 BRCA1 therapeutic NSMs had 328 cumulative breast-years of follow-up, with one ipsilateral cancer recurrence not directly involving the nipple or areola (0.0030 per breast-year); 237 BRCA2 prophylactic NSMs had 926 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0011 per breast-year); and 53 BRCA2 therapeutic NSMs had 239 cumulative breast-years of follow-up, with two ipsilateral recurrent cancers, neither of which directly involved the nipple or areola (0.0084 per breast-year). CONCLUSIONS: The risk of new ipsilateral breast cancers is extremely low after NSM in BRCA1 and BRCA2 mutation carriers. NSM is an effective risk-reducing strategy for BRCA gene mutations.

Smartphone Global Positioning System (GPS) Data Enhances Recovery Assessment After Breast Cancer Surgery.

PURPOSE: We sought to determine whether smartphone GPS data uncovered differences in recovery after breast-conserving surgery (BCS) and mastectomy, and how these data aligned with self-reported quality of life (QoL). METHODS: In a prospective pilot study, adult smartphone-owners undergoing breast surgery downloaded an application that continuously collected smartphone GPS data for 1 week preoperatively and 6 months postoperatively. QoL was assessed with the Short-Form-36 (SF36) via smartphone delivery preoperatively and 4 and 12 weeks postoperatively. Endpoints were trends in daily GPS-derived distance traveled and home time, as well as SF36 Physical (PCS) and Mental Component Scores (MCS) comparing BCS and mastectomy patients. RESULTS: Thirty-one patients were included. Sixteen BCS and fifteen mastectomy patients were followed for a mean of 201 (SD 161) and 174 (107) days, respectively. There were no baseline differences in demographics, PCS/MCS, home time, or distance traveled. Through 12 weeks postoperatively, mastectomy patients spent more time at home [e.g., week 4: 16.7 h 95% CI (14.3, 19.6) vs. 11.0 h (9.4, 12.9), p < 0.001] and traveled shorter distances [e.g., week 4: 52.5 km 95% CI (36.1, 76.0) vs. 107.7 km (75.8-152.9), p = 0.009] compared with BCS patients. There were no significant QoL differences throughout the study as measured by the MCS [e.g., week 4 difference: 7.83 95% CI (- 9.02, 24.7), p = 0.362] or PCS [e.g., week 4 difference: 8.14 (- 6.67, 22.9), p = 0.281]. GPS and QoL trends were uncorrelated (ρ < ± 0.26, p > 0.05). CONCLUSIONS: Differences in BCS and mastectomy recovery were successfully captured using smartphone GPS data. These data may describe currently unmeasured aspects of physical and mental recovery, which could supplement traditional and QoL outcomes to inform shared decision-making.

A system for risk stratification and prioritization of breast cancer surgeries delayed by the COVID-19 pandemic: preparing for re-entry.

PURPOSE: During the COVID-19 pandemic, most breast surgery for benign and malignant conditions has been postponed, creating a backlog of patients who will need surgery. A fair and transparent system for assessing the risk of further delaying surgery for individual patients to prioritize surgical scheduling is needed. METHODS: Factors related to risk of delaying surgery for breast patients were identified. Scores were assigned to each factor, with higher scores indicating a greater risk from delaying surgery. REDCap and Microsoft Excel tools were designed to track and score delayed patients. RESULTS: Published data and multidisciplinary clinical judgement were used to assign risk scores based on patient and tumor factors, length of delay, and tumor response to preoperative therapy. Patients completing neoadjuvant chemotherapy were assigned the highest scores as their options for delaying surgery are most limited. Among patients receiving neoadjuvant endocrine therapy or no medical therapy, higher scores were assigned for low-estrogen receptor or high-genomic risk scores, higher grade, larger tumors, younger age and longer delay. High priority scores were assigned for progression during preoperative therapy. Low scores were assigned for re-excisions, atypical lesions and other benign indications. There was good agreement of the tool's ranking of sample patients with rankings by experienced clinicians. The tool generates risk-stratified patient lists by surgeon or institution to facilitate assignment of surgery dates. CONCLUSIONS: This tool generates a clinically consistent, risk-stratified priority list of breast surgical procedures delayed by the COVID-19 pandemic. This systematic approach may facilitate surgical scheduling as conditions normalize.

Node-Positive Patients Treated with Neoadjuvant Chemotherapy Can Be Spared Axillary Lymph Node Dissection with Wireless Non-Radioactive Localizers.

BACKGROUND: Targeted axillary dissection (TAD) involves sentinel lymph node biopsy (SLNB) and excision of a biopsy-proven node marked by a clip. This study evaluates the feasibility of non-radioactive wireless localizers for targeted excision of clipped axillary lymph nodes. METHODS: We identified biopsy-proven, node-positive breast cancer patients treated with neoadjuvant therapy (NAT) and TAD from 2016 to 2020, and included those with a clipped node localized using SAVI SCOUT, Magseed, or RFID Tag. Primary outcome measures were (1) successful localization (ultrasound or mammographic-guided placement < 10 mm from target), and (2) retrieval of the clipped node during TAD, documented by specimen radiography or gross visualization. Secondary outcomes included rates of completion axillary lymph node dissection (cALND) and complications. RESULTS: Overall, 57 patients were included; 1 (1.8%) patient had no clip visible at the time of localization, and no radiographic confirmation of clip placement at the time of biopsy, and was therefore excluded. In the remaining 56 patients, localization was successful in 53 (94.6%) patients and the clipped node was retrieved during TAD in 51 (91.1%) patients. Twenty-three of 27 (85.2%) ypN0 patients were spared cALND; 3 (11.1%) patients had cALND for failed clipped node retrieval during TAD, and 1 (3.7%) for false-positive frozen section. In patients with TAD alone, the rates of axillary seroma and infection were 20.0% and 8.6%, respectively. CONCLUSIONS: Wireless non-radioactive localizers are feasible for axillary localization after NAT, with high success rates of retrieving clipped nodes. The lack of signal decay is an advantage of these devices, allowing flexibility in timing of placement.

Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery.

BACKGROUND: Obtaining tumor-free margins is critical to prevent recurrence after lumpectomy for breast cancer. Unfortunately, current approaches leave positive margins that require second surgeries in 20-40% of patients. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. METHODS: Breast lumpectomy cavity walls and excised specimens were assessed with the LUM Imaging System after 1 mg/kg intravenous LUM015, a protease-activatable fluorescent agent. Fluorescence at potential sites of residual tumor in lumpectomy cavity walls was evaluated intraoperatively with a sterile hand-held probe, with real-time predictive results displayed on a monitor intraoperatively, and later correlated with histopathology. RESULTS: In vivo lumpectomy cavities and excised specimens were imaged after LUM015 injection in 45 women undergoing breast cancer surgery. Invasive ductal and lobular cancers and intraductal cancer (DCIS) were included. A total of 570 cavity margin surfaces in 40 patients were used for algorithm development. Image analysis and display took approximately 1 s per 2.6-cm-diameter circular margin surface. All breast cancer subtypes could be distinguished from adjacent normal tissue. For all imaged cavity surfaces, sensitivity for tumor detection was 84%. Among 8 patients with positive margins after standard surgery, sensitivity for residual tumor detection was 100%; 2 of 8 were spared second surgeries because additional tissue was excised at sites of LUM015 signal. Specificity was 73%, with some benign tissues showing elevated fluorescent signal. CONCLUSIONS: The LUM015 agent and LUM Imaging System allow rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.

Correction to: Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery.

The article Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery, written by Barbara L. Smith et al., was originally published electronically on the publisher's internet portal on January 2, 2020, without open access.

Incidental breast carcinoma: incidence, management, and outcomes in 4804 bilateral reduction mammoplasties.

INTRODUCTION: Bilateral reduction mammoplasty is one of the most common plastic surgery procedures performed in the U.S. This study examines the incidence, management, and prognosis of incidental breast cancer identified in reduction specimens from a large cohort of reduction mammoplasty patients. METHODS: Breast pathology reports were retrospectively reviewed for evidence of incidental cancers in bilateral reduction mammoplasty specimens from five institutions between 1990 and 2017. RESULTS: A total of 4804 women met the inclusion criteria of this study; incidental cancer was identified in 45 breasts of 39 (0.8%) patients. Six patients (15%) had bilateral cancer. Overall, the maximum diagnosis by breast was 16 invasive cancers and 29 ductal carcinomas in situs. Thirty-three patients had unilateral cancer, 15 (45.5%) of which had high-risk lesions in the contralateral breast. Twenty-one patients underwent mastectomy (12 bilateral and nine unilateral), residual cancer was found in 10 in 25 (40%) therapeutic mastectomies. Seven patients did not undergo mastectomy received breast radiation. The median follow-up was 92 months. No local recurrences were observed in the patients undergoing mastectomy or radiation. Three of 11 (27%) patients who did not undergo mastectomy or radiation developed a local recurrence. The overall survival rate was 87.2% and disease-free survival was 82.1%. CONCLUSIONS: Patients undergoing reduction mammoplasty for macromastia have a small but definite risk of incidental breast cancer. The high rate of bilateral cancer, contralateral high-risk lesions, and residual disease at mastectomy mandates thorough pathologic evaluation and careful follow-up of these patients. Mastectomy or breast radiation is recommended for local control given the high likelihood of local recurrence without either.

Trends in Unilateral and Contralateral Prophylactic Mastectomy Use in Ductal Carcinoma In Situ of the Breast: Patterns and Predictors.

BACKGROUND: Increased use of contralateral prophylactic mastectomy (CPM) as treatment for ductal carcinoma in situ (DCIS) in the US was first noted in the early 2000s. Optimization of treatment guidelines for DCIS requires an understanding of current surgical treatment trends, particularly as they may differ by patient sociodemographic and community resource factors. OBJECTIVE: The aim of this study was to evaluate surgical treatment trends among US women with DCIS and to assess the impact of sociodemographic and community resource factors on surgical treatment choice. METHODS: The Surveillance, Epidemiology, and End Results dataset was queried for women aged 40 years and older who were diagnosed with unilateral DCIS between 2000 and 2014. Annual mastectomy rates were compared over time by age and race/ethnicity. Multivariable logistic regressions were performed to identify predictors of mastectomy use, with patient sociodemographics, tumor characteristics, and community resource factors (i.e. plastic surgeon density) as covariates. RESULTS: A total of 130,731 women with DCIS met the inclusion criteria. Overall mastectomy rates remained relatively unchanged over the study period (25-30%). CPM use increased for all age and race/ethnic groups, with the greatest increase exhibited by women aged 40-49 years [relative to 2000; 2014 odds ratio (OR) 10.6]. With respect to community resource factors, CPM use, as opposed to unilateral mastectomy, was associated with counties of higher education level (OR 1.52), higher income level (OR 1.22), and lower plastic surgeon density (OR 1.26). CONCLUSION AND RELEVANCE: While the popularity of mastectomy in the management of DCIS has remained relatively unchanged since the turn of the century, the use of CPM has risen substantially. Younger women with DCIS have seen the greatest increase in CPM use, a choice that remains influenced by race/ethnicity as well as income, education, and health resource availability. Until clinical risk stratifiers of DCIS are identified, the surgical decision-making paradigm must be improved so that treatment choice remains sensitive to cultural differences but becomes independent of income, education, and health resource availability.

Enhanced Recovery Minimizes Opioid Use and Hospital Stay for Patients Undergoing Mastectomy with Reconstruction.

BACKGROUND: This study examined the effects of an enhanced recovery program on inpatient opioid requirements and hospital length of stay (LOS) for mastectomy patients undergoing immediate reconstruction. METHODS: An enhanced recovery program for patients undergoing mastectomy with immediate tissue expander (TE) or implant reconstruction was evaluated by comparing a contemporary cohort of 611 patients in 2016-2018 with a historical cohort of 188 patients in 2010. Opioid use and LOS were compared over time and stratified by laterality, mastectomy type, axillary procedure, and reconstruction. Associations were assessed by uni- and multivariate analyses. RESULTS: In 2010, 95.2% of patients required intravenous (IV) opioids, with a last dose 15.5 h after completion of surgery, compared with 68.7% of patients in 2016-2018, with a last dose 1.8 h after surgery (p < 0.001). Patients prescribed gabapentin postoperatively were less likely to require inpatient IV or oral opioids (p < 0.001). The mean LOS decreased from 37 h in 2010 to 27.5 h in 2016-2018 without an increase in the readmission rate (6.9% vs. 4.1%; p = 0.112). Patients were more likely to stay more than one night if they were older (p = 0.012), had undergone bilateral mastectomies (p < 0.001) or TE reconstruction (p = 0.012), and had surgery in 2010 compared with 2016-2018 (p < 0.001). Even after adjustment for LOS, IV opioid use remained significantly associated with year of surgery (p < 0.001). CONCLUSIONS: Compared with 2010, patients undergoing mastectomy with TE or implant reconstruction in 2016-2018 required less inpatient opioids and had decreased LOS. The authors attribute this to an enhanced recovery program focused on preoperative counseling, non-opioid analgesics, and improved surgical efficiencies.

Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system.

PURPOSE: Obtaining tumor-free surgical margins is critical to prevent recurrence in breast-conserving surgery but it remains challenging. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. METHODS: Lumpectomy cavity walls and excised specimens of breast cancer lumpectomy patients were assessed with the LUM Imaging System (Lumicell, Inc., Wellesley MA) with and without intravenous LUM015, a cathepsin-activatable fluorescent agent. Fluorescence at potential sites of residual tumor was evaluated with a sterile hand-held probe, displayed on a monitor and correlated with histopathology. RESULTS: Background autofluorescence was assessed in excised specimens from 9 patients who did not receive LUM015. In vivo lumpectomy cavities and excised specimens were then imaged in 15 women undergoing breast cancer surgery who received no LUM015, 0.5, or 1 mg/kg LUM015 (5 women per dose). Among these, 11 patients had invasive carcinoma with ductal carcinoma in situ (DCIS) and 4 had only DCIS. Image acquisition took 1 s for each 2.6-cm-diameter surface. No significant background normal breast fluorescence was identified. Elevated fluorescent signal was seen from invasive cancers and DCIS. Mean tumor-to-normal signal ratios were 4.70 ± 1.23 at 0.5 mg/kg and 4.22 ± 0.9 at 1.0 mg/kg (p = 0.54). Tumor was distinguished from normal tissue in pre-and postmenopausal women and readings were not affected by breast density. Some benign tissues produced fluorescent signal with LUM015. CONCLUSION: The LUM Imaging System allows rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.

Reassessing risk models for atypical hyperplasia: age may not matter.

PURPOSE: The aim of this study was to investigate the influence of age at diagnosis of atypical hyperplasia ("atypia", ductal [ADH], lobular [ALH], or severe ADH) on the risk of developing subsequent invasive breast cancer or ductal carcinoma in situ (DCIS). METHODS: Using standard survival analysis methods, we retrospectively analyzed 1353 women not treated with chemoprevention among a cohort of 2370 women diagnosed with atypical hyperplasia to determine the risk relationship between age at diagnosis and subsequent breast cancer. RESULTS: For all atypia diagnoses combined, our cohort showed a 5-, 10-, and 15-year risk of invasive breast cancer or DCIS of 0.56, 1.25, and 1.30, respectively, with no significant difference in the (65,75] year age group. For women aged (35,75] years, we observed no significant difference in the 15-year risk of invasive breast cancer or DCIS after atypical hyperplasia, although the baseline risk for a 40-year-old woman is approximately 1/8 the risk of a 70-year-old woman. The risks associated with invasive breast cancer or DCIS for women in our cohort diagnosed with ADH, severe ADH, or ALH, regardless of age, were 7.6% (95% CI 5.9-9.3%) at 5 years, 25.1% (20.7-29.2%) at 10 years, and 40.1% (32.8-46.6%) at 15 years. CONCLUSION: In contrast to current risk prediction models (e.g., Gail, Tyrer-Cuzick) which assume that the risk of developing breast cancer increases in relation to age at diagnosis of atypia, we found the 15-year cancer risk in our cohort was not significantly different for women between the ages of 35 (excluded) and 75. This implies that the "hits" received by the breast tissue along the "high-risk pathway" to cancer might possibly supersede other factors such as age.

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. CONCLUSIONS: Our 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.

JOURNAL CLUB: Diagnostic Utility of MRI After Negative or Inconclusive Mammography for the Evaluation of Pathologic Nipple Discharge.

OBJECTIVE: The purpose of this study is to determine the diagnostic utility of MRI after negative or inconclusive mammography for the evaluation of pathologic nipple discharge. MATERIALS AND METHODS: We conducted a retrospective review of breast MRI examinations from January 1, 2006, through December 31, 2015, that were performed after negative or inconclusive mammography for the evaluation of nipple discharge. Clinical notes, imaging findings, and pathology outcomes were reviewed. RESULTS: One hundred eighteen women (mean age, 49 years; range, 23-82 years) underwent MRI for evaluation of nipple discharge, 105 (89.0%) of whom had surgical excision or at least 2-year imaging follow-up. A total of six patients (6/105; 5.7%) were diagnosed with malignancy (ductal carcinoma in situ [DCIS] or invasive malignancy). Of 27 patients with positive MRI findings (final assessment of BI-RADS category 4), three (11.1%) were diagnosed with malignancy: DCIS grade 2-3, DCIS with focus of microinvasive ductal carcinoma, and invasive papillary carcinoma. An additional three patients (without suspicious findings at MRI) were diagnosed with malignancy at surgical excision, all of which were grade 1 DCIS. For patients with negative MRI findings (BI-RADS category 1, 2, or 3), the negative predictive value of MRI for malignancy was 96.2% (75/78). CONCLUSION: In women with nipple discharge and negative or inconclusive mammography findings, the risk of malignancy is low, at 5.7%. With negative MRI findings (BI-RADS category 1, 2, or 3), the risk of malignancy is less than 4%. Surveillance rather than surgical excision may be a reasonable option for patients without suspicious findings at MRI.

Factors Associated with Recurrence Rates and Long-Term Survival in Women Diagnosed with Breast Cancer Ages 40 and Younger.

BACKGROUND: Young age at breast cancer diagnosis has been associated with increased risk of recurrence and mortality. We reevaluated this assumption in a large, modern cohort of women diagnosed with breast cancer at age ≤40 years. METHODS: We identified women with breast cancer at age ≤40 years at a single institution from 1996-2008. We assessed locoregional recurrence (LRR), distant recurrence, disease-free survival (DFS), and overall survival (OS), and correlated patient and tumor characteristics with outcomes. RESULTS: We identified 584 women aged ≤40 years with breast cancer. Median age was 37 years, and median follow-up was 124 months; 61.5 % were stages 0-I and 38.5 % were stages II-III. Overall, 57.4 % had lumpectomies and 42.5 % mastectomies. DFS was 93 % at 5 years and 84.5 % at 10 years. OS was 93 % at 5 years and 86.5 % at 10 years. On multivariate analysis, worse DFS was associated with positive nodes (p = 0.002); worse OS was associated with larger tumor size (p = 0.042). When stratified by lumpectomy versus mastectomy, there were no significant differences in survival or recurrence. For lumpectomy patients, DFS was 96 % at 5 years and 88 % at 10 years; OS was 96 % at 5 years and 89 % at 10 years. For mastectomy patients, DFS was 89.5 % at 5 years and 79 % at 10 years; OS was 90 % at 5 years and 83 % at 10 years. Lumpectomy LRR rates were 1 % at 5 years and 4 % at 10 years. Mastectomy LRR rates were 3.5 % at 5 years and 8.7 % at 10 years. CONCLUSIONS: Outcomes for women with breast cancer at age ≤40 years have improved. Lumpectomy recurrence rates are low, suggesting that lumpectomy is oncologically safe for young breast cancer patients.