Breast Conservation Surgery and Mastectomy Have Similar Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From 1462 Patients on the Prospective, Randomized I-SPY2 Trial.

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.

Pregnancy-associated breast cancer: does timing of presentation affect outcome?

PURPOSE: Pregnancy-associated breast cancer (PABC) comprises breast cancer diagnosed during the gestational period or within 12 months postpartum. While the incidence of PABC appears to be increasing, data regarding prognosis remain limited. METHODS: Here we evaluate clinicopathologic features, treatments, and clinical outcomes among women with stage 0-III PABC diagnosed between 1992 and 2020. Comparisons were made between women who were diagnosed with PABC during gestation and those who were diagnosed within 12 months postpartum. RESULTS: A total of 341 women were identified, with a median age of 36 years (range 25-46). The pregnancy group comprised 119 (35%) women, while 222 (65%) women made up the postpartum group. Clinicopathologic features were similar between groups, with most patients being parous and presenting with stage I and II disease. Treatment delays were uncommon, with a median time from histologic diagnosis to treatment of 4 weeks for both groups. Recurrence-free survival was similar between groups: 67% at 10 years for both. While 10-year overall survival appeared higher in the postpartum group (83% versus 78%, p = 0.02), only the presence of nodal metastases was associated with an increased risk of death (hazard ratio 5.61, 95% CI 2.20-14.3, p < 0.001), whereas timing of diagnosis and receptor profile did not reach statistical significance. CONCLUSION: Clinicopathologic features of women with PABC are similar regardless of timing of diagnosis. While 10-year recurrence-free survival is similar between groups, 10-year overall survival is higher among women diagnosed postpartum; however, timing of diagnosis may not be the driving factor in determining survival outcomes.

Insufficient Reporting of Race and Ethnicity in Breast Cancer Clinical Trials.

BACKGROUND: Reporting race and ethnicity in clinical trial publications is critical for determining the generalizability and effectiveness of new treatments. This is particularly important for breast cancer, in which Black women have been shown to have between 40 and 100% higher mortality rate yet are underrepresented in trials. Our objective was to describe changes over time in the reporting of race/ethnicity in breast trial publications. PATIENTS AND METHODS: We searched ClinicalTrials.gov to identify the primary publication linked to trials with results posted from May 2010-2022. Statistical analysis included summed frequencies and a linear regression model of the proportion of articles reporting race/ethnicity and the proportion of non-White enrollees over time. RESULTS: A proportion of 72 of the 98 (73.4%) studies that met inclusion criteria reported race/ethnicity. In a linear regression model of the proportion of studies reporting race/ethnicity as a function of time, there was no statistically significant change, although we detected a signal toward a decreasing trend (coefficient for quarter = -2.2, p = 0.2). Among all studies reporting race and ethnicity over the study period, the overall percentage of non-White enrollees during the study period was 21.9%, [standard error (s.e.) 1.8, 95% confidence interval (CI) 18.4, 25.5] with a signal towards a decreasing trend in Non-White enrollment [coefficient for year-quarter = -0.8 (p = 0.2)]. CONCLUSION: Our data demonstrate that both race reporting and overall representation of minority groups in breast cancer clinical trials did not improve over the last 12 years and may have, in fact, decreased. Increased reporting of race and ethnicity data forces the medical community to confront disparities in access to clinical trials. This may improve efforts to recruit and retain members of minority groups in clinical trials, and over time, reduce racial disparities in oncologic outcomes.

The Landmark Series-Addressing Disparities in Breast Cancer Screening: New Recommendations for Black Women.

Randomized, clinical trials have established the efficacy of screening mammography in improving survival from breast cancer for women through detection of early, asymptomatic disease. However, disparities in survival rates between black women and women from other racial and ethnic groups following breast cancer diagnosis persist. Various professional groups have different, somewhat conflicting, guidelines with regards to recommended age for commencing screening as well as recommended frequency of screening exams, but the trials upon which these recommendations are based were not specifically designed to examine benefit among black women. Furthermore, these recommendations do not appear to incorporate the unique epidemiological circumstances of breast cancer among black women, including higher rates of diagnosis before age 40 years and greater likelihood of advanced stage at diagnosis, into their formulation. In this review, we examined the epidemiologic and socioeconomic factors that are associated with breast cancer among black women and assess the implications of these factors for screening in this population. Specifically, we recommend that by no later than age 25 years, all black women should undergo baseline assessment for future risk of breast cancer utilizing a model that incorporates race (e.g., Breast Cancer Risk Assessment Tool [BCRAT], formerly the Gail model) and that this assessment should be conducted by a breast specialist or a healthcare provider (e.g., primary care physician or gynecologist) who is trained to assess breast cancer risk and is aware of the increased risks of early (i.e., premenopausal) and biologically aggressive (e.g., late-stage, triple-negative) breast cancer among black women.

Association of Moderate-Risk Breast Cancer Genes with Contralateral Prophylactic Mastectomy and Bilateral Disease.

BACKGROUND: The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known. METHODS: Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer. RESULTS: The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138). CONCLUSIONS: Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

The Role of Safety-Net Hospitals in Reducing Disparities in Breast Cancer Care.

Advances in breast cancer screening and systemic therapies have been credited with profound improvements in breast cancer outcomes; indeed, 5-year relative survival rate approaches 91% in the USA (U.S. National Institutes of Health NCI. SEER Training Modules, Breast). While breast cancer mortality has been declining, oncologic outcomes have not improved equally among all races and ethnicities. Many factors have been implicated in breast cancer disparities; chief among them is limited access to care which contributes to lower rates of timely screening mammography and, once diagnosed with breast cancer, lower rates of receipt of guideline concordant care (Wu, Lund, Kimmick GG et al. in J Clin Oncol 30(2):142-150, 2012). Hospitals with a safety-net mission, such as the essential hospitals, historically have been dedicated to providing high-quality care to all populations and have eagerly embraced the role of caring for the most vulnerable and working to eliminate health disparities. In this article, we review landmark articles that have evaluated the role safety-net hospitals have played in providing equitable breast cancer care including to those patients who face significant social and economic challenges.

Timing of Presentation and Outcomes of Women with Stage IV Pregnancy-Associated Breast Cancer (PABC).

BACKGROUND: Pregnancy-associated breast cancer (PABC) and concurrent, or early development of, stage IV disease is uncommon. Given this rarity, and complexities surrounding pregnancy, data are limited regarding PABC treatment and outcomes. We evaluated oncologic, obstetric, and fetal outcomes of women with stage IV PABC in relation to presentation timing and treatment. PATIENTS AND METHODS: Our retrospective review of an institutional database identified women with stage IV PABC from 1998 to 2018. PABC was defined as diagnosis during pregnancy or ≤ 1 year postpartum. Clinicopathologic, treatment, and outcome variables were compared between women diagnosed during pregnancy versus postpartum. RESULTS: We identified 77 women (median age 35 years; interquartile range [IQR] 32-37 years): 51 (66%) in the postpartum group and 26 (34%) in the pregnant group, including 9 with therapeutic or spontaneous abortion. Among 17 women who continued pregnancy, no obstetric or fetal complications were noted. Clinicopathologic and treatment variables did not differ between groups. Of 43 women dead from disease, 15 had triple negative (TN) tumors. Median overall survival (OS) of TN tumors was 14 months (range 5-39 months); OS was associated with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2) positive tumors (p < 0.01). At 31 months (range 0-137 months) median follow-up, the 5-year OS was 34% (95% confidence interval 21-46%), and did not differ among pregnant and postpartum groups (p = 0.2). CONCLUSIONS: Women with stage IV TN PABC had high mortality rates despite multimodality therapy. Timing of presentation did not affect management decisions or OS, even for women who completed pregnancy. Further research to understand PABC biology, focusing on TN tumors, is warranted.

Fertility Preservation in Young Women with Breast Cancer: Impact on Treatment and Outcomes.

BACKGROUND: The impact of chemotherapy timing on the fertility preservation (FP) decision is poorly understood. Here we evaluate factors associated with FP completion among women age ≤ 45 years with breast cancer who received chemotherapy and consulted with a reproductive endocrinology and infertility (REI) specialist, and report pregnancy and oncologic outcomes. PATIENTS AND METHODS: This retrospective review included all women age ≤ 45 years diagnosed with stage I-III unilateral breast cancer at Memorial Sloan Kettering Cancer Center between 2009 and 2015 who received chemotherapy and consulted with an REI specialist. Clinicopathologic features and factors associated with the decision to undergo FP were analyzed, and comparisons were made with the Wilcoxon rank-sum test, Chi-square test, or Fisher's exact test. Survival curves were constructed using the Kaplan-Meier method. RESULTS: Among the 172 women identified, median age was 34 years (interquartile range 31-37 years). The majority of women were single (n = 99, 57.6%) and nulliparous (n = 134, 77.9%). Most women underwent FP (n = 121, 70.3%). Factors associated with the decision to undergo FP included younger median age (33 vs. 37 years, p < 0.001), having private insurance (p < 0.001), nulliparity (p < 0.001), and referral from Breast Surgery (p = 0.004). Tumor characteristics and treatments were similar between women who underwent FP and those who declined. Overall survival and recurrence-free survival were also similar between groups. Women who underwent FP were more likely to have a biological child after breast cancer treatment. CONCLUSIONS: Women underwent FP at high rates independent of timing of chemotherapy and oncologic factors. FP is associated with having a biological child and does not compromise oncologic outcomes.

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.

Does Failure to Achieve Pathologic Complete Response with Neoadjuvant Chemotherapy Identify Node-Negative Patients Who Would Benefit from Postmastectomy Radiation or Regional Nodal Irradiation?

BACKGROUND: Postmastectomy radiation (PMRT) and regional nodal irradiation (RNI) improve outcomes for patients at high risk of locoregional recurrence (LRR). Node-negative patients with the triple-negative (TN) subtype and those who do not have a pCR with neoadjuvant chemotherapy (NAC) are at increased risk for LRR, but whether the absolute risk for LRR is high enough to justify PMRT/RNI is uncertain. METHODS: Patients with cT1-T3N0 and pN0 disease treated with NAC who had residual disease in the breast were identified from a prospective database. Patients were eligible for the study if they had mastectomy or breast-conserving therapy with negative margins and whole-breast radiation. Those receiving PMRT or RNI were excluded. Actuarial rates were estimated using the cumulative incidence function. RESULTS: The 227 patients in this study had a mean age was 51.4 ± 12.6 years, and 82 (36.1%) were TN. During a median follow-up period of 35 months, nine LRR events occurred. The overall crude and actuarial 3-year LRR rates were 4.4% and 5.9%, respectively. The crude LRR rate for the TN patients was 7.4%, and the 3-year actuarial rate was 10.1%. The hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) patients had a crude LRR rate of 2.8% and a 3-year actuarial rate of 3.2%. The HER2+ patients had a crude LRR rate of 2.7% and a 3-year actuarial rate of 3.3%. CONCLUSIONS: Locoregional recurrence is uncommon for patients with node-negative HR+/HER2- and HER2+ tumors who have residual disease in the breast; however, TN patients have LRR rates that approach 10% at 3 years, suggesting a possible role for PMRT/RNI for node-negative TN patients. Additional follow-up with more patients is needed for definitive conclusions.

Palpable Adenopathy Does Not Indicate High-Volume Axillary Nodal Disease in Hormone Receptor-Positive Breast Cancer.

BACKGROUND: Axillary metastases in the form of palpable adenopathy indicate the need for neoadjuvant chemotherapy or axillary lymph node dissection (ALND). Patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) disease infrequently have nodal pathologic complete response to neoadjuvant chemotherapy and often require ALND. Sentinel lymph node biopsy is an accepted treatment for patients with two or fewer non-palpable nodal metastases who are undergoing breast conservation. The proportion of patients with HR+/HER2- disease with palpable adenopathy and two or fewer nodal metastases is unknown. METHODS: Patients with cT1-T3N1 HR+/HER2- disease with palpable adenopathy were identified from a prospective database. Patients who underwent mastectomy or breast-conserving therapy with ALND were included in this study, whereas patients who received neoadjuvant chemotherapy were excluded. Clinicopathologic characteristics were compared between patients with two or fewer or more than two positive nodes on ALND. RESULTS: Of 180 patients included, 78 (43%) had two or fewer positive nodes on ALND, including 40/72 patients (56%) who underwent lumpectomy. On univariate analysis, cT1 tumor, unifocal tumor, only one palpable node, and two or fewer suspicious nodes on ultrasound were associated with two or fewer positive nodes on ALND. On multivariable analysis, number of suspicious nodes on ultrasound and cT stage were independently associated with two or fewer positive nodes on ALND. CONCLUSIONS: A substantial minority of patients with cT1-3N1 HR+/HER2- disease with palpable adenopathy had two or fewer positive nodes on ALND. Standard clinicopathologic features and ultrasound findings can help identify candidates for upfront sentinel lymph node biopsy as a strategy to avoid ALND. Prospective studies evaluating this approach are warranted.

Oncoplastic Breast-Conserving Surgery: Can We Reduce Rates of Mastectomy and Chemotherapy Use in Patients with Traditional Indications for Mastectomy?

INTRODUCTION: Traditional indications for mastectomy include multiple ipsilateral lesions and/or disease spanning ≥ 5 cm. Neoadjuvant chemotherapy increases breast conservation but does not improve survival. We hypothesized that oncoplastic breast-conserving surgery (OPS) may allow for breast conservation while providing full staging and tumor profiling information to guide systemic therapy decisions, thereby permitting more judicious chemotherapy use. METHODS: This was an observational cohort of patients with invasive breast cancer with multiple lesions and/or disease spanning ≥ 5 cm who underwent OPS from 2012 to 2018. Clinicopathologic features, mastectomy rate, chemotherapy use, and recurrence were evaluated. RESULTS: Overall, 100 patients were identified. Average disease span was 62.8 ± 20.1 mm, with an average of 2.9 lesions (range 1-13). 'No ink on tumor' was achieved at the index operation in 80 patients; 13 patients underwent completion mastectomy to achieve adequate margins. Eighty-one patients completed radiation therapy. Breast conservation was possible in 50/58 (86%) patients who did not receive chemotherapy. Forty-two patients received chemotherapy (8 neoadjuvant, 34 adjuvant), of whom 37 (88%) achieved breast conservation. Twenty-six patients with high-risk features received adjuvant chemotherapy. Oncotype DX testing demonstrated the need for chemotherapy in an additional eight patients. After a median follow-up of 40 months, four patients had a local recurrence, including two who declined radiation therapy. CONCLUSIONS: OPS can facilitate breast conservation in most patients with traditional indications for mastectomy. Additionally, OPS may reduce unnecessary chemotherapy, especially in patients who qualify for Oncotype DX testing. Further study evaluating long-term oncologic and cosmetic outcomes is warranted.

Evaluating Need for Additional Imaging and Biopsy After Oncoplastic Breast-Conserving Surgery.

INTRODUCTION: Breast-conserving therapy (BCT) using oncoplastic surgery (OPS) allows for larger resections and improved aesthetics though volume redistribution and tissue rearrangement. Data regarding the impact of OPS on surveillance imaging and need for additional biopsies are limited. METHODS: This observational cohort underwent BCT at a single institution from 2009 to 2018; standard breast-conserving surgery (BCS) was the predominant approach until OPS was introduced in 2012. Rates of imaging beyond standard diagnostic views, as well as rates of biopsy following both approaches, are reported. RESULTS: A total of 422 consecutive patients were identified. The OPS group comprised 205 patients and the BCS group included 217 patients. There was no difference in need for additional imaging between groups (BCS: 58 patients [26.7%] vs. OPS: 53 patients [25.9%]; p = 0.91). When additional imaging was required, it was on the ipsilateral side in 35 (60.3%) BCS patients compared with 24 (45.3%) OPS patients (p = 0.21). The need for biopsy was higher in the BCS group (BCS: 41 patients [18.9%] with 47 total biopsies vs. OPS: 20 patients [9.3%] with 22 total biopsies; p < 0.01). Benign findings on biopsy were similar between groups (BCS: 18 [38.3%] vs. OPS: 11 [50.0%]; p = 0.66). CONCLUSIONS: OPS was not associated with an increased need for additional imaging compared with BCS. Concern regarding challenges with follow-up imaging should not impact the decision to offer OPS. Further study and longer-term follow-up is warranted to understand the trends in need for additional imaging, biopsy, and additional procedures following OPS.

Does Use of Neoadjuvant Chemotherapy Affect the Decision to Pursue Fertility Preservation Options in Young Women with Breast Cancer?

BACKGROUND: The American Society of Clinical Oncology guidelines recommend early referral to reproductive endocrinology and infertility (REI) specialists for young women diagnosed with breast cancer. Current practice patterns demonstrate an increased utilization of neoadjuvant chemotherapy (NAC). We evaluated premenopausal women with breast cancer after consultation with a Fertility Nurse Specialist (FNS) and determine factors associated with referral to REI specialists. METHODS: This retrospective review included all premenopausal women diagnosed at our institution with stage 0-III unilateral breast cancers between 2009 and 2015 who completed an FNS consultation. Clinicopathologic features and factors associated with referral to REI after FNS consultation were analyzed. RESULTS: A total of 334 women were identified. Median age was 35 years (interquartile range 32-38). The majority of women were single (n = 198, 59.3%) and nulliparous (n = 239, 71.6%). REI referrals were common (n = 237, 71.0%). The Breast Surgery service was the most frequent referring service (n = 194, 58.1%), with significantly more REI referrals compared to Breast Medicine and Genetics services (p = 0.002). Nulliparity was associated with REI referral (p < 0.0001). Adjuvant chemotherapy (p = 0.003) was associated with pursuing REI referral, whereas NAC (p < 0.001) was associated with declining REI referral. CONCLUSIONS: Most women elected to consult with an REI specialist, confirming strong interest in fertility preservation among premenopausal women with breast cancer. However, women receiving NAC more frequently declined referral to REI, suggesting that the need to start NAC may influence decisions regarding fertility preservation. With increasing utilization of NAC, our study supports the need for further counseling and education regarding fertility preservation for women undergoing NAC.

Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs. METHODS: A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS). RESULTS: High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04). CONCLUSION: High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. PATIENTS AND METHODS: A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). RESULTS: The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006]. CONCLUSIONS: Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

Impact of initial imaging with gallium-68 dotatate PET/CT on diagnosis and management of patients with neuroendocrine tumors.

BACKGROUND: Somatostatin analog functional imaging with gallium-68 (Ga-68) dotatate positron emission tomography/computed tomography (PET/CT) has demonstrated superiority in lesion detection in patients with neuroendocrine tumors (NETs). The clinical impact of this imaging modality on US surgical and medical oncology practices has not been established. METHODS: Consecutive patients with NET at our institution who received an initial Ga-68 dotatate PET/CT between July 2017 and September 2018 were included. Ga-68 dotatate PET/CT was compared with prior imaging. RESULTS: Among 101 eligible patients, 51 of 50 were female/male, site of origin was gastroenteropancreatic (75%), unknown primary (13%), lung (8%), thymus (2%), and other (2%). All NETs were histologically well/moderately differentiated. Ga-68 dotatate imaging findings altered management in 36 (35.6%) patients: documentation of progression led to the initiation of systemic therapy in 14 patients, obviated the need for biopsy in four patients, and altered surgical plans in 7 of 14 (50%) patients referred for surgery. In 11 patients, decisions regarding peptide receptor radionucleotide therapy and somatostatin analogs were altered. CONCLUSIONS: In this series, Ga-68 dotatate PET/CT altered diagnosis and management in one-third of patients and changed operative plans in half of the patients who were referred for surgical evaluation. These results support the routine use of this imaging in the care of patients with early-stage and advanced NETs.

Adjuvant therapy following resection of gastroenteropancreatic neuroendocrine tumors provides no recurrence or survival benefit.

BACKGROUND AND OBJECTIVES: Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use. METHODS: Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts. RESULTS: In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P < .01). RFS with somatostatin analog therapy (compared to none) was lower (P < .01), as was OS (P = .01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P < .01). CONCLUSIONS: Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.

Oncoplastic breast-conserving therapy and intraoperative radiotherapy for management of carcinoma in situ of the breast: A single-center experience.

Intraoperative radiation therapy (IORT) has been shown to reduce local recurrence rates among women with early-stage invasive ductal carcinoma, but data regarding its use among women with in situ carcinoma are limited. In this single-institution study, 50 women with in situ carcinoma were treated with oncoplastic breast-conserving surgery (OPS) and single-dose IORT. All 50 patients had "no tumor on ink," but 9 (16%) had margins < 2 mm and required additional therapy. No local recurrences were observed after a median follow-up of 46 months. Single-dose IORT is an efficacious treatment for well-selected patients with DCIS.