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.

Predictors of Reexcision following Breast-Conserving Surgery for Ductal Carcinoma In Situ.

BACKGROUND: Reexcision following breast-conserving surgery (BCS) in women with ductal carcinoma in situ (DCIS) results in adjuvant treatment delays, higher health care costs, and undesirable cosmetic outcomes. The purpose of this study is to determine patient, imaging, pathological, and surgical predictors of reexcision following BCS for DCIS. PATIENTS AND METHODS: A retrospective review of women with DCIS who had BCS from 2007 to 2016 was conducted. Patient, imaging, pathological, and surgical features, in addition to surgical outcomes, were collected from medical records. Standard statistical tests were used to compare features between patients who did and did not undergo at least one reexcision. A multivariable logistic regression model was fit to assess features associated with reexcision. RESULTS: A total of 547 women (mean age 59 years; range 30-88 years) diagnosed with DCIS at core needle biopsy underwent BCS. Of all women, 31.6% (173/547) had at least one reexcision. With multivariable analysis, features associated with reexcision included younger patient age (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.97-1.0, p = 0.049), African-American race (aOR 2.66, 95% CI 1.13-6.26, p = 0.03), biopsy modality of ultrasound (aOR 2.35, 95% CI 1.22-4.53, p = 0.01), and earlier year of surgery (aOR 0.92, 95% CI 0.86-0.98, p = 0.01). No pathological features of DCIS were associated with reexcision risk. CONCLUSIONS: In our cohort of nearly 550 women with DCIS who underwent BCS, 31.6% had at least one reexcision. Features associated with reexcision include younger patient age, African-American race, biopsy modality of ultrasound, and earlier year of surgery.

Do Eligibility Criteria for Ductal Carcinoma In Situ (DCIS) Active Surveillance Trials Identify Patients at Low Risk for Upgrade to Invasive Carcinoma?

BACKGROUND: Clinical trials are currently ongoing to determine the safety and efficacy of active surveillance (AS) versus usual care (surgical and radiation treatment) for women with ductal carcinoma in situ (DCIS). This study aimed to determine upgrade rates of DCIS at needle biopsy to invasive carcinoma at surgery among women who meet the eligibility criteria for AS trials. METHODS: A retrospective review was performed of consecutive women at an academic medical center with a diagnosis of DCIS at needle biopsy from 2007 to 2016. Medical records were reviewed for mode of presentation, imaging findings, biopsy pathology results, and surgical outcomes. Each patient with DCIS was evaluated for AS trial eligibility based on published criteria for the COMET, LORD, and LORIS trials. RESULTS: During a 10-year period, DCIS was diagnosed in 858 women (mean age 58 years; range 28-89 years). Of the 858 women, 498 (58%) were eligible for the COMET trial, 101 (11.8%) for the LORD trial, and 343 (40%) for the LORIS trial. The rates of upgrade to invasive carcinoma were 12% (60/498) for the COMET trial, 5% (5/101) for the LORD trial, and 11.1% (38/343) for the LORIS trial. The invasive carcinomas ranged from 0.2 to 20 mm, and all were node-negative. CONCLUSIONS: Women who meet the eligibility criteria for DCIS AS trials remain at risk for occult invasive carcinoma at presentation, with upgrade rates ranging from 5 to 12%. These findings suggest that more precise criteria are needed to ensure that women with invasive carcinoma are excluded from AS trials.

Ductal carcinoma in situ on digital mammography versus digital breast tomosynthesis: rates and predictors of pathologic upgrade.

OBJECTIVES: To compare upgrade rates of ductal carcinoma in situ (DCIS) on digital mammography (DM) versus digital breast tomosynthesis (DBT) and identify patient, imaging, and pathological features associated with upgrade risk. METHODS: A retrospective review was performed of 318 women (mean 59 years, range 37-89) with screening-detected DCIS from 2007 to 2011 (DM group) and from 2013 to 2016 (DBT group). Comparisons made between DM and DBT groups using the unpaired t test and chi-square test include detection rates of DCIS, upgrade rates to invasive cancer, and pathological features of DCIS and upgraded cases. Patient, imaging, and pathological features associated with upgrade were also determined. P values < 0.05 were considered significant. RESULTS: There was no significant difference in detection rates of DCIS between DM and DBT groups (0.9 versus 1.0 per 1000 examinations, p = 0.45). Upgrade rates of DCIS to invasive cancer in DM and DBT groups were similar (17.3% versus 16.8%, p = 0.90), despite significant differences in pathological features of DCIS between DM and DBT groups (including nuclear grade, comedonecrosis, and progesterone receptor status [p ≤ 0.01]). Among upgraded cases, a higher proportion were high-grade invasive cancers with DBT (36.7% versus 9.5%, p = 0.03). In both groups, ultrasound-guided (versus stereotactic) biopsy was associated with higher upgrade risk (p ≤ 0.03). CONCLUSIONS: There was no significant difference in detection rates or upgrade rates of DCIS on DM versus DBT; however, upgraded cases were more likely to be high grade with DBT, suggesting possible differences in tumor biology between cancers with DM and DBT. In both DM and DBT groups, biopsy modality was associated with upgrade risk. KEY POINTS: • Detection rates and upgrade rates of ductal carcinoma in situ (DCIS) on digital mammography (DM) versus digital breast tomosynthesis (DBT) are similar. • A higher proportion of upgraded cases were high-grade invasive cancers with DBT than DM, suggesting possible differences in tumor biology between cancers that are detected with DM and DBT. • With both DM and DBT, ultrasound-guided biopsy (versus stereotactic biopsy) was associated with a higher risk of upgrade.

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.

Breast cancer screening patterns among military beneficiaries: racial variations in screening eliminated in an equal-access model.

BACKGROUND: African American women present with more aggressive breast tumors and at later stages than white women. Many factors have been proposed to explain these findings, including socioeconomic status, cultural beliefs, and access to medical care. The purpose of this project was to determine if stage at presentation would be equivalent in a system providing equal access to care and if screening was equivalent. METHODS: The Naval Medical Center San Diego (NMCSD) tumor registry from 2007 to 2012 was queried for this cross-sectional study. Eligible women included all those diagnosed and treated for breast cancer at NMCSD. Distribution of tumor stage (early vs. advanced) between racial groups was compared by age, treatment, and receptor status. RESULTS: A total of 624 women were eligible; 88 % were early stage (0-II) and 12 % presented with advanced stage (III or IV). Racial differences in distribution were significant among African American and Hispanic women for early versus advanced presentation (p = 0.011). No racial disparity was seen in screening patterns among women. CONCLUSIONS: In a military health system with equal access to care and standard screening recommendations, screening patterns did not vary with race but did vary with stage and active duty status. African American women present with breast cancer at later stages and with more hormone-receptor negative tumors, suggesting that biology rather than socioeconomic or access factors may be the most important determinant of stage at presentation of breast cancer for African American women.

Minority-Serving Hospitals Are Associated With Low Within-Hospital Disparity.

BACKGROUND: Disparities in obstetric care have been well documented, but disparities in the within-hospital population have not been as extensively explored. The objective is to assess cesarean delivery rate disparities at the hospital level in a nationally recognized low risk of cesarean delivery group. METHODS: An observational study using a national population-based database, Nationwide Inpatient Sample, from 2008 to 2011 was conducted. All patients with nulliparous, term, singleton, vertex pregnancies from Black and White patients were included. The primary outcome was delivery mode (cesarean vs vaginal). The primary independent variable was race (Black vs White). RESULTS: A total of 1,064,351 patients were included and the overall nulliparous, term, singleton, and vertex pregnancies cesarean delivery rate was 14.1%. The within-hospital disparities of cesarean delivery rates were lower in minority-serving hospitals (OR: 1.20 95% CI: 1.12-1.28), rural hospitals (OR 1.11 95% CI: 1.02-1.20), and the South (OR 1.24 95% CI 1.19-1.30) compared to their respective counterparts. Non-minority serving hospitals (OR: 1.20 95% CI 0.12-1.25), and urban hospitals (OR1.32 95% CI 1.28-1.37), the Northeast (OR 1.41 95% CI 1.30-1.53) or West (OR 1.52 95% CI 1.38-1.67), had higher within-hospital racial disparities of cesarean delivery rates. The odds ratios reported are comparing within-hospital cesarean delivery rates in Black and White patients. DISCUSSION: Significant within-hospital disparities of cesarean delivery rates across hospitals highlight the importance of facility-level factors. Policies aimed at advancing health equity must address hospital-level drivers of disparities in addition to structural racism.

Time to surgery: A health equity metric in breast cancer patients.

BACKGROUND: We evaluated whether time to surgery by race can be a health equity metric of surgical access. METHODS: An observational analysis was performed using the National Cancer Database from 2010 to 2019. Inclusion criteria were women with stage I-III breast cancer. We excluded women with multiple cancers and whose diagnosis was made at a different hospital. The primary outcome variable was surgery within 90 days of diagnosis. RESULTS: A total of 886,840 patients were analyzed, with 76.8% White and 11.7% Black patients. 11.9% of patients experienced delayed surgery, which was significantly more common in Black patients than White patients. On adjusted analysis, Black patients were still significantly less likely to receive surgery within 90 days when compared to White patients (OR 0.61, 95% CI 0.58-0.63). CONCLUSION: The delay in surgery experienced by Black patients highlights the contribution of system factors in cancer inequity and should be a focus for targeted interventions.

Contralateral breast cancer after curative-intent treatment for ductal carcinoma in situ: Rate and associated clinicopathological and imaging risk factors.

PURPOSE: Patients who have ductal carcinoma in situ (DCIS) are undergoing bilateral mastectomy at increasing rates. One of the reasons is to minimize contralateral breast cancer (CBC) risk. The purpose of this study is to determine the rate of and risk factors associated with CBC in women treated for DCIS. METHODS: A retrospective study was performed of women with DCIS at surgery from 2007 to 2014 who had at least five-year follow-up. Patient attributes, imaging findings, histopathology results, and surgical and long-term outcomes were collected. Features associated with a CBC were assessed with multivariable logistic regression models. RESULTS: 613 women (mean 56 years, range 30-87) with DCIS underwent breast-conserving surgery (BCS) (n = 426), unilateral mastectomy (n = 101), or bilateral mastectomy (n = 86), with mean follow-up of 7.9 years. Of the 527 women who had BCS or unilateral mastectomy, 7.4% (n = 39) developed a CBC (DCIS in 12 and invasive cancer in 27). 4.1% (5/122) of women treated with adjuvant endocrine therapy developed a CBC, compared to 8.4% (34/405) who were not treated (p = .11). Features associated with CBC risk were younger age at menarche (adjusted odds ratio [aOR] of 0.76, p = .03) and low nuclear grade of DCIS (aOR of 5.43 for grade 1 versus 3, p = .01). CONCLUSION: In women treated for DCIS, the overall rate of CBC was low at 7.4%. Younger age at menarche and low nuclear grade of DCIS had significant associations with higher CBC risk.

Predicting ipsilateral recurrence in women treated for ductal carcinoma in situ using machine learning and multivariable logistic regression models.

PURPOSE: To develop machine learning (ML) and multivariable regression models to predict ipsilateral breast event (IBE) risk after ductal carcinoma in situ (DCIS) treatment. METHODS: A retrospective investigation was conducted of patients diagnosed with DCIS from 2007 to 2014 who were followed for a minimum of five years after treatment. Data about each patient were extracted from the medical records. Two ML models (penalized logistic regression and random forest) and a multivariable logistic regression model were developed to evaluate recurrence-related variables. RESULTS: 650 women (mean age 56 years, range 27-87 years) underwent treatment for DCIS and were followed for at least five years after treatment (mean 8.0 years). 5.5% (n = 36) experienced an IBE. With multivariable analysis, the variables associated with higher IBE risk were younger age (adjusted odds ratio [aOR] 0.96, p = 0.02), dense breasts at mammography (aOR 3.02, p = 0.02), and < 5 years of endocrine therapy (aOR 4.48, p = 0.02). The multivariable regression model to predict IBE risk achieved an area under the receiver operating characteristic curve (AUC) of 0.75 (95% CI 0.67-0.84). The penalized logistic regression and random forest models achieved mean AUCs of 0.52 (95% CI 0.42-0.61) and 0.54 (95% CI 0.43-0.65), respectively. CONCLUSION: Variables associated with higher IBE risk after DCIS treatment include younger age, dense breasts, and <5 years of adjuvant endocrine therapy. The multivariable logistic regression model attained the highest AUC (0.75), suggesting that regression models have a critical role in risk prediction for patients with DCIS.

Diversity efforts in surgery: Are we there yet?

INTRODUCTION: We aimed to assess and quantify recent efforts of surgical departments in achieving diversity, equity and inclusion. METHODS: Chairs of surgery at US hospitals were identified from a database maintained by the Association of Women Surgeons and surveyed to assess diversity, equity and inclusion efforts. RESULTS: A total of 226 surveys were sent out with a 22.6% response rate. Across all survey respondents, only 28.2% of surgeons were female and 24.4% were URiM, with no programs reporting any non-binary surgeons. In the last 3 years, 95.8% programs reported an increase in female surgeons, while only 75.5% programs reported an increase in URiM surgeons. Program size made no difference in diversity across race or gender. DISCUSSION: Recent recruitment efforts are bringing change to departments of surgery. Retaining diverse faculty, ensuring equity in promotions, and giving every faculty the opportunity to thrive is essential to fostering diversity, equity and inclusion in surgery.

Symptomatic ductal carcinoma in situ (DCIS): Upstaging risk and predictors.

PURPOSE: To estimate the upstaging risk of symptomatic ductal carcinoma in situ (DCIS) to invasive disease and to identify features related to upstaging risk. MATERIALS AND METHODS: This retrospective investigation includes symptomatic women with DCIS at core needle biopsy from January 2007 to December 2016 at a large academic institution. Patient characteristics, findings at imaging, core needle biopsy histopathology results, and final surgical histopathology results were retrieved from the medical records. Using standard statistical tests, patient, imaging, and pathology features were compared between DCIS cases that were upstaged to invasive disease at surgery versus cases that were not upstaged. RESULTS: From 2007 to 2016, fewer than 5% (63/1399) of women diagnosed with DCIS presented with symptoms. Therefore, 63 women (mean age, 51; range, 27-88 years) comprised the study cohort. 84.1% (n = 53) presented with an area of clinical concern, and 15.9% (n = 10) presented with pathologic nipple discharge. The most common finding at mammography was calcifications with or without an associated asymmetry or mass (74.1%, 40/54). The upstaging rate of symptomatic DCIS to invasive disease was 34.9% (22/63). Imaging modality used for biopsy was associated with higher upstaging risk, with cases that were biopsied under MRI guidance accounting for 22.7% of upstaged cases versus 4.9% of non-upstaged cases (p = 0.03). CONCLUSIONS: Women with DCIS uncommonly present with symptoms, and the upstaging rate of symptomatic DCIS is high at nearly 35%. Biopsy modality type of MRI is associated with higher upstaging risk.

Noncalcified Ductal Carcinoma In Situ (DCIS): Rate and Predictors of Upgrade to Invasive Carcinoma.

RATIONALE AND OBJECTIVES: To determine the upgrade rate of noncalcified ductal carcinoma in situ (DCIS) and features that are associated with risk of upgrade to invasive disease at surgery. MATERIALS AND METHODS: A retrospective review was conducted of consecutive women who were diagnosed with noncalcified DCIS from January 2007 to December 2016. Patient demographics, imaging findings, biopsy pathology results, and surgical outcomes were reviewed. The unpaired t test, chi-square test, and Fisher's exact test were used to compare features between the cases of DCIS that did and did not upgrade to invasive carcinoma at surgery. RESULTS: Over a 10-year period, 78 women (mean age 62 years, range 30-88 years) were diagnosed with noncalcified DCIS. Two-thirds (67.9%, 53/78) of cases were detected on screening mammography, and 15.4% (12/78) of diagnoses were made after presentation with an area of palpable concern. The most common mammographic presentations of noncalcified DCIS were mass (51.3%, 40/78) and asymmetry (30.8%, 24/78). Seventeen cases (21.8%, 17/78) were upgraded to invasive ductal carcinoma (IDC) at surgery. Features associated with upgrade risk included older patient age (68.1 versus 60.3 years, OR 1.08, p < 0.01) and family history of breast cancer in a first-degree relative (41.2% [7/17] versus 16.4% [10/61], OR 3.57, p = 0.03). CONCLUSION: In our study cohort, the upgrade rate of noncalcified DCIS to IDC at surgery is 21.8%. Upgrade risk is associated with older patient age and family history of breast cancer in a first-degree relative.

Pre-operative MRI in patients with ductal carcinoma in situ: Is MRI useful for identifying additional disease?

PURPOSE: To determine if pre-operative MRI is useful for identifying additional disease that would impact surgical management in women with ductal carcinoma in situ (DCIS). METHODS: We conducted a retrospective review of consecutive women with calcifications at mammography yielding DCIS at core biopsy from 2007 to 2016 who subsequently underwent MRI examinations. Patient characteristics, imaging findings, and pathology outcomes were collected from the medical records. Standard statistical tests were used to compare the patients who underwent MRI examinations (MRI group) and those who did not (no MRI group). RESULTS: 963 women (age 58 years, range 28-89 years) presented with calcifications that yielded DCIS at biopsy, of whom 236 (24.5 %) underwent MRI examinations. The MRI group was younger, less likely to have a prior breast cancer, and more likely to have dense breasts than the no MRI group (all p < 0.001). 66 women (28.0 %) had 80 MRI findings that were recommended for work-up and/or biopsy. 21 patients had 23 MRI findings that were not pursued pre-operatively, and 45 patients with 57 MRI findings underwent biopsy. The positive predictive value of biopsies performed (PPV3) was 45.6 % (26/57). 26 cancers were detected in 24 women; thus, MRI detected additional sites of cancer in 11.2 % (24/215) of patients. Of the 26 cancers, 13 (50.0 %) were DCIS and 13 (50.0 %) were invasive. CONCLUSIONS: MRI in selected women with DCIS identified additional sites of disease in 11.2 % and thus could be considered in the pre-operative evaluation of this specific patient cohort.