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.

Racially Conscious Cancer Screening Guidelines: A Path Towards Culturally Competent Science.

OBJECTIVE: To review the racial composition of the study populations that the current USPSTF screening guidelines for lung, breast, and colorectal cancer are based on, and the effects of their application across non-white individuals. SUMMARY OF BACKGROUND DATA: USPSTF guidelines commonly become the basis for establishing standards of care, yet providers are often unaware of the racial composition of the study populations they are based on. METHODS: We accessed the USPSTF screening guidelines for lung, breast, and colorectal cancer via their website, and reviewed all referenced publications for randomized controlled trials (RCTs), focusing on the racial composition of their study populations. We then used PubMed to identify publications addressing the generalizability of such guidelines across non-white individuals. Lastly, we reviewed all guidelines published by non-USPSTF organizations to identify the availability of race-specific recommendations. RESULTS: Most RCTs used as basis for the current USPSTF guidelines either did not report race, or enrolled cohorts that were not representative of the U.S. population. Several studies were identified demonstrating the broad application of such guidelines across non-white individuals can lead to underdiagnosis and higher levels of advanced disease. Nearly all guideline-issuing bodies fail to provide race-specific recommendations, despite often acknowledging increased disease burden among non-whites. CONCLUSION: Concerted efforts to overcome limitations in the generalizability of RCTs are required to provide screening guidelines that are truly applicable to non-white populations. Broader policy changes to improve the pipeline for minority populations into science and medicine are needed to address the ongoing lack of diversity in these fields.

The Role of Race and Gender in the Career Experiences of Black/African American Academic Surgeons: A Survey of the Society of Black Academic Surgeons and a Call to Action.

OBJECTIVE: To determine the role of race and gender in the career experience of Black/AA academic surgeons and to quantify the prevalence of experience with racial and gender bias stratified by gender. SUMMARY OF BACKGROUND DATA: Compared to their male counterparts, Black/African American women remain significantly underrepresented among senior surgical faculty and department leadership. The impact of racial and gender bias on the academic and professional trajectory of Black/AA women surgeons has not been well-studied. METHODS: A cross-sectional survey regarding demographics, employment, and perceived barriers to career advancement was distributed via email to faculty surgeon members of the Society of Black American Surgeons (SBAS) in September 2019. RESULTS: Of 181 faculty members, 53 responded (29%), including 31 women (58%) and 22 men (42%). Academic positions as a first job were common (men 95% vs women 77%, P = 0.06). Men were more likely to attain the rank of full professor (men 41% vs women 7%, P = 0.01). Reports of racial bias in the workplace were similar (women 84% vs men 86%, not significant); however, reports of gender bias (women 97% vs men 27%, P < 0.001) and perception of salary inequities (women 89% vs 63%, P = 0.02) were more common among women. CONCLUSIONS AND RELEVANCE: Despite efforts to increase diversity, high rates of racial bias persist in the workplace. Black/AA women also report experiencing a high rate of gender bias and challenges in academic promotion.

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.

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.

Uptake of Breast Cancer Clinical Trials at Minority Serving Cancer Centers.

BACKGROUND: Most minorities receive cancer care at minority-serving hospitals (MSHs) that have been associated with disparate treatment between Black and White patients. OBJECTIVE: Our aim was to examine the uptake of clinical trials that have changed axillary management in breast cancer patients at MSH and non-MSH cancer centers. METHODS: The National Cancer Database was used to identify patients eligible for the American College of Surgeons Oncology Group Z0011 and Z1071 trials, and mastectomy patients fulfilling the European AMAROS trial. Uptake of trial results (omission of axillary lymph node dissection) was analyzed between patients treated at MSHs and non-MSHs and adjusted for patient, tumor, and facility factors. MSHs were defined as the top decile of hospitals according to the proportion of Black and Hispanic patients treated. RESULTS: Of 7167 patients eligible for Z0011, 4546 for Z0171, and 9433 for AMAROS from 2015 to 2016, clinical trial uptake was seen in 1195 (74.6%) MSH and 4056 (72.9%) non-MSH patients (p = 0.173) for Z0011, 588 (41.9%) MSH and 1366 (43.5%) non-MSH patients for Z1071 (p = 0.302), and 272 (11.7%) MSH and 996 (14.0%) non-MSH patients (p = 0.005) for AMAROS. On adjusted analyses, MSH status was not significant for uptake of any of the three trials. Black race, socioeconomic status, and insurance were not associated with clinical trial uptake. CONCLUSION: The uptake of three landmark clinical trials of axillary management in breast cancer was not different at MSH and non-MSH centers despite adjustment for social determinants of health. At the Commission on Cancer-accredited centers in this analysis, MSH status did not affect the uptake of evidence-based care.

A Call to Action: Black/African American Women Surgeon Scientists, Where are They?

OBJECTIVE: To determine the representation of Black/AA women surgeons in academic medicine among U.S. medical school faculty and to assess the number of NIH grants awarded to Black/AA women surgeon-scientists over the past 2 decades. SUMMARY OF BACKGROUND DATA: Despite increasing ethnic/racial and sex diversity in U.S. medical schools and residencies, Black/AA women have historically been underrepresented in academic surgery. METHODS: A retrospective review of the Association of American Medical Colleges 2017 Faculty Roster was performed and the number of grants awarded to surgeons from the NIH (1998-2017) was obtained. Data from the Association of American Medical Colleges included the total number of medical school surgery faculty, academic rank, tenure status, and department Chair roles. Descriptive statistics were performed. RESULTS: Of the 15,671 U.S. medical school surgical faculty, 123 (0.79%) were Black/AA women surgeons with only 11 (0.54%) being tenured faculty. When stratified by academic rank, 15 (12%) Black/AA women surgeons were instructors, 73 (59%) were assistant professors, 19 (15%) were associate professors, and 10 (8%) were full professors of surgery. Of the 372 U.S. department Chairs of surgery, none were Black/AA women. Of the 9139 NIH grants awarded to academic surgeons from 1998 and 2017, 31 (0.34%) grants were awarded to fewer than 12 Black/AA women surgeons. CONCLUSION: A significant disparity in the number of Black/AA women in academic surgery exists with few attaining promotion to the rank of professor with tenure and none ascending to the role of department Chair of surgery. Identifying and removing structural barriers to promotion, NIH grant funding, and academic advancement of Black/AA women as leaders and surgeon-scientists is needed.

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.

Disparities in timely surgery among Asian American women with breast cancer.

BACKGROUND: We investigated the likelihood of timely surgery for breast cancer patients among diverse Asian subgroups. METHODS: We analyzed the National Cancer Database from 2010 to 2019 and included White and Asian women diagnosed with stage I-III breast cancer. Patients with multiple cancers, patients who received chemotherapy, and those diagnosed and treated at different hospitals were excluded. The primary outcome was timely surgery within 8 weeks of diagnosis. Race was the primary independent variable. Asian Americans were stratified by geography. RESULTS: A total of 716,701 women were analyzed, with 3.5% Asians. Delayed surgery was experienced by 13.2% of women. Adjusted analysis indicated no difference in receiving timely surgery between all Asians and Whites. However, Southeast Asians were less likely to undergo timely surgery compared to Whites (OR 0.75, 95% CI 0.67-0.84). CONCLUSIONS: Variations among Asian ethnicities emphasize the need to explore treatment patterns to address disparities in breast cancer care.

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.

Axillary Recurrence in Sentinel Lymph Node Negative Mastectomy Patients at 16 Years Median Follow Up: Natural History in the Absence of Radiation.

BACKGROUND: Axillary recurrence following lumpectomy with a negative sentinel lymph node biopsy (SLNB) is rare, possibly due to routine use of whole breast radiation. In this study, we characterized the rate of any axillary recurrence among mastectomy patients with a negative SLNB and no adjuvant radiation therapy. METHODS: We identified women who underwent mastectomy with SLNB for early-stage breast cancer (1999-2005) and included patients with pathologically negative nodes and no axillary dissection or adjuvant radiation. The primary outcome was ipsilateral axillary recurrence. RESULTS: A total of 234 women, median age 50 years, underwent 242 mastectomies. Histology showed 112 (46%) invasive cancers, 16 (7%) ductal carcinoma in-situ (DCIS) with microinvasion, and 114 (47%) pure DCIS. Cancers were predominantly estrogen receptor positive (59%) and moderate (41%) or high grade (32%). A mean of 2 final sentinel nodes were excised (range 1-6) and 21 patients (9%) had isolated tumor cells on SLNB pathology. At 16 years median follow up (range 1-22 years), 3 patients (1.2%) developed an isolated axillary failure, and 1 had concurrent axillary and chest wall recurrences (total axillary recurrence rate 1.7%). Three of four axillary recurrences occurred in patients with moderate or high-grade estrogen receptor-positive DCIS without invasion on mastectomy histology. Median time to axillary recurrence was 70.5 months (range 29-132 months). CONCLUSIONS: Axillary recurrence is rare after a negative SLNB, even in the absence of adjuvant radiation. This supports the safety of forgoing additional surgery or radiation to the axilla in the early-stage breast cancer and a negative SLNB.