Other Primary Malignancies in Patients with Breast Cancer Who Undergo Germline Panel Testing.

BACKGROUND: Women with a history of breast cancer (BC) more commonly have a diagnosis of other primary malignancies (OPMs) than the general population. This study sought to evaluate OPMs among patients with BC who underwent germline testing with a hereditary BC gene panel. METHODS: The study identified women 18 years of age or older with a history of unilateral BC who underwent multi-gene panel testing between January 2014 and August 2019 at the authors' institution. Patient, tumor, and treatment factors for BC and OPM diagnoses were collected for descriptive, univariate, and overall survival (OS) analyses. RESULTS: Among 1163 patients, 330 (28.4%) had an OPM. The median follow-up period was 4.1 years from BC diagnosis. Of the 1163 patients, 209 (18%) had a BRCA pathogenic variant (PV), 306 (26.4%) had a non-BRCA PV, and 648 (55.7%) had no PV. Development of an OPM varied according to germline testing result, with an OPM developing for 18.6% (39/209) of the patients with a BRCA PV, 31.8% (204/648) of the patients with no PV, and 28.4% (87/306) of the patients with a non-BRCA PV (p < 0.0001). The most common OPMs were ovarian (n = 60), uterine (n = 44), sarcoma (n = 36), melanoma (n = 27), colorectal (n = 22), and lymphoma (n = 20) malignancies. The 5-year OS was 96%. The patients with an OPM 5 years after BC diagnosis had a shorter OS than those who did not (93.4% vs 97.5%; p = 0.002). CONCLUSION: More than 25% of women with BC who underwent germline panel testing had an OPM diagnosed during the short-term follow-up period, and the diagnosis of an OPM was associated with reduced OS. These data have implications for counseling BC patients who undergo germline testing regarding future cancer screening.

Current Considerations in Surgical Treatment for Adolescents and Young Women with Breast Cancer.

Adolescents and young women (AYA) with breast cancer represent a unique patient population, compared to the general population with breast cancer. We performed a literature review to evaluate the factors that influenced the surgical outcomes in this patient population. Fifty-two studies were identified, which evaluated breast surgery type, axillary surgery, contralateral prophylactic mastectomy (CPM), surgical timing, psychological factors, disparities, and imaging use. AYA patients had equivalent oncologic outcomes with breast conserving surgery (BCS) or mastectomy. CPM did not improve survival. There are limited data on axillary management in the AYA population, and while more data would be beneficial, this is currently extrapolated from the general breast cancer population. A shorter time to initiate treatment correlated to better outcomes, and disparities need to be overcome for optimal outcomes. AYA patients appreciated involvement in clinical decisions, and shared decision making should be considered whenever possible. Providers must keep these factors in mind when counseling AYA patients, regarding the surgical management of breast cancer.

Impact of the early COVID-19 pandemic on Breast Surgical Oncology fellow education.

INTRODUCTION: The early COVID-19 pandemic rapidly transformed healthcare and medical education. We sought to evaluate the professional and personal impact of the pandemic on 2019-2020 Breast Surgical Oncology (BSO) fellows in Society of Surgical Oncology approved programs to capture the experience and direct future changes. METHODS: From July 15, 2020 to August 4, 2020 a survey was administered to the American Society of Breast Surgeons' fellow members. The survey assessed the impact of the pandemic on clinical experience, education/research opportunities, personal health/well-being, and future career. Responses were collected and aggregated to quantify the collective experience of respondents. RESULTS: Twenty-eight of fifty-seven (54%) eligible fellows responded. Twenty-one (75%) indicated the clinical experience changed. Twenty-seven (96%) reported less time spent caring for ambulatory breast patients and sixteen (57%) reported the same/more time spent in the operating room. Fourteen (50%) stated their future job was impacted and eight (29%) delayed general surgery board examinations. Stress was increased in 26 (93%). Personal health was unaffected in 20 (71%), and 3 (10%) quarantined for COVID-19 exposure/infection. CONCLUSION: The COVID-19 pandemic altered the clinical experience of BSO fellows; however, the operative experience was generally unaffected. The creation of frameworks and support mechanisms to mitigate potential challenges for fellows and fellowship programs in the ongoing pandemic and other times of national crisis should be considered.

Sentinel Lymph Node Removal After Neoadjuvant Chemotherapy in Clinically Node-Negative Patients: When to Stop?

BACKGROUND: The maximum number of sentinel lymph nodes (SLN) to be resected to accurately stage the axilla in patients undergoing neoadjuvant chemotherapy (NAC) for the treatment of clinically node-negative (cN0) breast cancer has not been determined. We sought to determine the sequence of removal of the positive SLNs in this patient population. METHODS: All patients aged ≥ 18 years diagnosed with cN0 invasive breast cancer who received NAC and underwent SLN surgery at Mayo Clinic Rochester between September 2008 and September 2018 were identified. Univariate analysis was performed to compare factors associated with positive nodes and where the first positive node was in the sequence of removal of the SLNs. RESULTS: We identified 446 cancers among 440 patients with a median age of 51 (IQR: 43, 61) years. At surgery, 381 (85.4%) cancers were pathologically node (ypN) negative and 65 (14.6%) were pN + . The number of nodes removed was similar for both patients with ypN0 and ypN + disease, with a median number of SLNs removed of 2.0 (IQR: 2.0, 3.0). Of all patients with a positive node, the first positive node was most commonly the 1st node removed (75.4%), and was identified by the 3rd SLN removed in all cases. CONCLUSIONS: Among cN0 patients treated with NAC, if a positive SLN is present, it is most commonly identified as the 1st sentinel node removed by the surgeon, and was identified by the 3rd sentinel node in our series. This suggests that once 3 SLNs have been resected, removal of additional sentinel lymph nodes does not add diagnostic value.

Contralateral Risk-Reducing Mastectomy in Breast Cancer Patients Who Undergo Multigene Panel Testing.

BACKGROUND: An increasing number of breast cancer patients are undergoing expanded genetic testing and are being identified as germline mutation carriers. We sought to determine rates of contralateral risk-reducing mastectomy (CRRM) in patients with various germline mutations. PATIENTS AND METHODS: All women ≥ 18 years of age with unilateral breast cancer who underwent multigene panel testing between January 1, 2014 and August 1, 2019 at our academic institution were identified. Demographic, tumor, and treatment variables were identified from the medical record. Multivariable analyses were performed to compare factors associated with performance of CRRM. RESULTS: We identified 1613 patients, of whom 28.1% had a pathogenic variant and 40.1% had variants of uncertain significance (VUS). Overall, 420 patients (26.0%) underwent a CRRM. On multivariable analysis, factors associated with CRRM included age < 50 years (OR 3.8, 95% CI 3.0, 5.0), race (OR 0.5, 95% CI 0.3, 0.7 and OR 0.4, 95% CI 0.2, 0.7 for Black and Asian women, respectively, versus White women), and the presence of any germline mutation or VUS (OR 13.2, 95% CI 8.7, 20.2 for BRCA1/2; OR 3.9, 95% CI 2.7, 5.8 for non-BRCA germline mutation; and OR 1.8, 95% CI 1.3, 2.6 for VUS). CONCLUSIONS: In breast cancer patients who undergo multigene panel testing, a sizeable number of women with pathogenic non-BRCA germline findings are opting for CRRM. Given that the risk of contralateral breast cancer in women with most pathogenic mutations other than BRCA1/2 remains poorly characterized, these data have implications for risk counseling and for ascertaining the true risks of contralateral breast cancer in this population.

Adolescents and Young Adults with Breast Cancer have More Aggressive Disease and Treatment Than Patients in Their Forties.

BACKGROUND: Adolescents and young adults (AYAs; age < 40 years) account for less than 2% of breast cancer patients. Therefore, little is known about the tumor characteristics and care provided to AYA patients. This study sought to describe demographic, tumor, and treatment variables among AYA patients. METHODS: The study identified patients ages 15 to 49 years with breast cancer between 2010 and 2015 from the National Cancer Database. Patient and tumor factors were compared using Chi-square tests. Multivariable logistic regression was used to model the effect of age group on treatment while adjusting for confounding variables. RESULTS: The study identified 46,265 AYA patients with stages 0 to 3 breast cancer and compared them with 169,423 breast cancer patients ages 40 to 49 years. A greater proportion of the AYA patients presented with clinical stage 2 or 3 disease than the adult patients 40 to 49 years old (stage 2 disease: 44.3% vs 29.9%, respectively; stage 3 disease: 14.0% vs 7.7%, respectively; both p < 0.001). A greater proportion of the AYA patients had triple-negative breast cancer (TNBC) or human epidermal growth factor receptor 2-positive (HER2+) cancer than the adult patients (TNBC: 21.2% vs 13.8%, respectively; HER2+: 26.0% vs 18.6%, respectively; both p < 0.001). Among the AYA patients, the very young (ages 15-29 years) had more advanced disease and TNBC or HER2+ disease than the older youth (ages 30 to 39 years). The multivariable analysis showed that the AYA patients were more likely to undergo mastectomy (odds ratio [OR] 2.1) and receive chemotherapy (OR 1.9) than patients in their forties (both p < 0.001). CONCLUSION: A greater proportion of the AYA breast cancer patients had more advanced disease and TNBC and HER2+ disease. The AYA patients had higher rates of mastectomy and use of chemotherapy than the adult breast cancer patients, reflecting that more aggressive therapy is recommended or chosen for women in this age group.

Pain and opioid prescriptions vary by procedure after breast surgery.

BACKGROUND: With the opioid epidemic in the United States, evaluating opioid prescribing patterns is essential. We evaluated opioids prescribed at discharge following breast surgery and their association with patient factors and pain scores. METHODS: We retrospectively identified adult patients who underwent a mastectomy for cancer at Mayo Clinic sites from January 2010 to December 2016. Pain scores and prescription data were compared across operations and patient factors by univariate and multivariable analyses. RESULTS: Of 4021 patients, 3782 (94.1%) received an opioid prescription. Median oral milligram morphine equivalents (MME) were similar across all site-specific procedure groups (medians ranging from 225 to 375) while pain scores ranged from 1 to 4. Patients undergoing bilateral mastectomy (BM) and immediate breast reconstruction (IBR) reported the greatest pain scores. Pain scores did not vary with age or diagnosis for patients undergoing unilateral mastectomy or BM with lymph node surgery and IBR procedures. On multivariable analysis, variables associated with a MME discharge prescription >Q4 values included age, body mass index, site, year, inpatient status, and pain before discharge >3. CONCLUSION: Patient-reported pain following breast surgery varied by procedure, while MMEs prescribed remained similar. This suggests current opioid prescribing does not reflect intensity of pain and requires further research to optimize discharge opioid prescribing practices.

99mTc-Tilmanocept Versus 99mTc-Sulfur Colloid in Lymphoscintigraphy: Sentinel Lymph Node Identification and Patient-Reported Pain.

Lymphoscintigraphy plays a vital role in sentinel lymph node (SLN) identification in oncologic breast surgery. The effectiveness of SLN localization and the degree of patient pain were compared between filtered 99mTc-sulfur colloid (99mTc-SC) and 99mTc-tilmanocept. Methods: A retrospective review of patients undergoing lymphoscintigraphy for breast cancer using 99mTc-SC (June 1, 2010, to December 31, 2011) or 99mTc-tilmanocept (June 1, 2013, to January 31, 2014) was performed. SLN appearance time and uptake, SLN pathology, proportion of positive SLNs removed, and pain scores were compared for each radiopharmaceutical using the χ2 test, Fisher exact test, and unequal variance t test, as appropriate. Results: In total, 76 patients, with 86 evaluated axillae, underwent lymphoscintigraphy: 29 with 99mTc-SC and 47 with 99mTc-tilmanocept. The mean SLN appearance time was 11.0 min for 99mTc-SC and 19.3 min for 99mTc-tilmanocept (P = 0.003). There was no difference in the mean transit uptake percentage: 2.2% for 99mTc-SC and 1.9% for 99mTc-tilmanocept (P = 0.55). 99mTc-tilmanocept identified a greater proportion of intraoperative blue nodes than did 99mTc-SC (P = 0.03). There was no significant difference between 99mTc-SC and 99mTc-tilmanocept in the number of SLNs removed, number of patients with positive SLNs, or pain score. Conclusion: 99mTc-SC use in lymphoscintigraphy is an acceptable alternative to 99mTc-tilmanocept for SLN detection in breast cancer, on the basis of the similarity in intraoperative SLN identification and pain scores.

Returns to the operating room after breast surgery at a tertiary care medical center.

BACKGROUND: Evaluation of returns to the operating room (RORs) may spur practice modifications to improve patient outcomes and hospital practices. We determined the frequency and indications for RORs after breast operations. METHODS: We identified patients ≥18 years who underwent a breast operation at our institution 1/1/14-1/13/17 and assessed ROR within 45-days. RORs were categorized as unplanned/planned, staged/unstaged, or unrelated procedures. Univariate and multivariable analyses compared variables between patients who did and did not have an ROR. RESULTS: 2,914 patients underwent a breast operation of whom 117 (4.0%) had 121 RORs. Planned staged procedures accounted for 48 RORs (39.7%), while unplanned complications accounted for 65 (53.7%). On multivariable analysis, ROR was more common among patients undergoing total, skin-sparing, or nipple-sparing mastectomy (versus lumpectomy) all p < 0.03, while immediate breast reconstruction did not increase RORs. CONCLUSIONS: RORs following breast operations occurred in 4% of patients, with approximately one-third for a staged oncologic procedure. Implementation of ROR documentation tools should be encouraged, as these data provide benchmarks for clinical practice improvement initiatives to improve the quality of patient care.

Patient-reported experience after outpatient breast surgery.

BACKGROUND: Given the growing emphasis on patient-centered care, we determined contributory factors to a positive experience among patients undergoing outpatient breast procedures. METHODS: We retrospectively identified patients ≥18 years-old who underwent a breast operation 7/2015-12/2016 and completed a survey within two weeks. Univariate analyses evaluated associations of factors with top survey composite measures. Key driver analysis identified top-priority survey factors for improving the overall assessment measure. RESULTS: Of 270 patients, patients who gave a top surgeon score were older (mean 62.5 vs 58.6 years, p = 0.048), more likely to report a pain score of 0 before discharge (87% vs 68%, p < 0.01), and were 30.8 times more likely to give a top rating overall (p < 0.01) than those who gave a lower surgeon score. Key driver analysis identified personal issues as the main target for improvement. CONCLUSION: To achieve top outpatient ratings, providers should focus on personal issues, including pain control, especially in younger patients. Surgeons should consider focusing on involving the patient in treatment decisions and emphasizing pain control and overall needs to improve the patient experience.

Validation of the American Association for the Surgery of Trauma's emergency general surgery breast infection grading system.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) developed emergency general surgery (EGS) grading systems for multiple diseases to standardize classification of disease severity. The grading system for breast infections has not been validated. We aimed to validate the AAST breast infection grading system. METHODS: Multi-institutional retrospective review of all adult patients with a breast infection diagnosis at Mayo Clinic Rochester 1/2015-10/2015 and Pietermaritzburg South African Hospital 1/2010-4/2016 was performed. AAST EGS grades were assigned by two independent reviewers. Inter-rater reliability was measured using the agreement statistic (kappa). Final AAST grade was correlated with patient and treatment factors using Pearson's correlation coefficient. RESULTS: Two hundred twenty-five patients were identified: grade I (n = 152, 67.6%), II (n = 44, 19.6%), III (n = 25, 11.1%), IV (n = 0, 0.0%), and V (n = 4, 1.8%). At Mayo Clinic Rochester, AAST grades ranged from I-III. The kappa was 1.0, demonstrating 100% agreement between reviewers. Within the South African patients, grades included II, III, and V, with a kappa of 0.34, due to issues of the grading system application to this patient population. Treatment received correlated with AAST grade; less severe breast infections (grade I-II) received more oral antibiotics (correlation [-0.23, P = 0.0004]), however, higher AAST grades (III) received more intravenous antibiotics (correlation 0.29, P <0.0001). CONCLUSIONS: The AAST EGS breast infection grading system demonstrates reliability and ease for disease classification, and correlates with required treatment, in patients presenting with low-to-moderate severity infections at an academic medical center; however, it needs further refinement before being applicable to patients with more severe disease presenting for treatment in low-/middle-income countries.

Breast Cancer Litigation in the 21st Century.

BACKGROUND: Approximately 15% of general surgeons practicing in the United States face a medical malpractice lawsuit each year. This study aimed to determine the reasons for litigation for breast cancer care during the past 17 years by reviewing a public legal database. METHODS: The LexisNexis legal database was queried using a comprehensive list of terms related to breast cancer, identifying all cases from 2000 to 2017. Data were abstracted, and descriptive analyses were performed. RESULTS: The study identified 264 cases of litigation pertaining to breast cancer care. Delay in breast cancer diagnosis was the most common reason for litigation (n = 156, 59.1%), followed by improperly performed procedures (n = 26, 9.8%). The medical specialties most frequently named in lawsuits as primary defendants were radiology (n = 76, 28.8%), general surgery (n = 74, 28%), and primary care (n = 52, 19.7%). The verdict favored the defendant in 145 cases (54.9%) and the plantiff in 60 cases (22.7%). In 59 cases (22.3%), a settlement was reached out of court. The median plaintiff verdict payouts ($1,485,000) were greater than the settlement payouts ($862,500) (p = 0.04). CONCLUSION: Failure to diagnose breast cancer in a timely manner was the most common reason for litigation related to breast cancer care in the United States. General surgery was the second most common specialty named in the malpractice cases studied. Most cases were decided in favor of the defendant, but when the plaintiff received a payout, the amount often was substantial. Identifying the most common reasons for litigation may help decrease this rate and improve the patient experience.

Minimal cosmetic revision required after minimally invasive pectus repair.

BACKGROUND: Despite surgical correction procedures for pectus deformities, remaining cosmetic asymmetry may have significant psychological effects. We sought to evaluate factors associated with plastic surgery (PS) consultation and procedures for these deformities at an academic institution. METHODS: We reviewed patients aged 0-21 diagnosed with a pectus excavatum or carinatum deformity at our institution between January 2001 and October 2016. Pectus diagnoses were identified by ICD-9/ICD-10 codes and surgical repair by CPT codes; patients receiving PS consultation were identified by clinical note service codes. Student's t tests, Fisher's exact tests, and Chi-squared tests were utilized. RESULTS: 2158 patients were diagnosed with a pectus deformity; 442 (20.4%) underwent surgical correction. 19/442 (4.3%) sought PS consultation, either for pectus excavatum [14/19 (73.7%)], carinatum [4/19 (21.0%)], and both [1/19 (5.3%)], (p = 0.02). Patients seeking PS consultation were more likely to be female (p < 0.01), have scoliosis (p = 0.02), or undergo an open repair (p < 0.01). The need for PS consultation did not correlate with Haller index, p = 0.78. CONCLUSION: PS consultation associated with pectus deformity repair was rare, occurring in < 5% of patients undergoing repair. Patients who consulted PS more commonly included females, patients with scoliosis, and those undergoing open repair. These patients would likely benefit most from multidisciplinary pre-operative discussions regarding repair of the global deformity.

Management of the axilla in metaplastic breast carcinoma.

BACKGROUND: Metaplastic breast cancer (MBC), characterized by admixed epithelial, squamous or mesenchymal elements, constitutes <1% of breast cancers and has a poor prognosis but a paradoxically low reported rate of axillary lymph node (LN) involvement. Due to its rarity, data on appropriate axillary management is lacking, prompting this investigation of LN status and outcomes. METHODS: We identified 41 MBC patients treated at our institution 2001-2011 who were followed for a median of 66 months. Statistical analyses evaluated axillary ultrasound (AUS), fine needle aspiration (FNA), and sentinel LN biopsy (SLNB) in association with LN status. RESULTS: Median tumor size was 2.7 cm and 76% were triple-negative. Twenty-three patients (56%) had preoperative AUS: 9 (39%) showed ≥1 suspicious LN, 6 proceeded to LN FNA and 3 were confirmed positive. Six patients had neoadjuvant chemotherapy, including 2 FNA LN+. Ten patients were LN+ at operation. Among 19 patients undergoing AUS and axillary surgery, AUS ± FNA sensitivity was 100% and specificity was 94%. LN positivity correlated with increasing tumor size, grade and angiolymphatic invasion. 16 patients recurred, 63% with distant disease (10/16) and one with isolated axillary disease after a negative SLNB not preceded by AUS. Overall SLNB accuracy was 96% (23/24), but absent preoperative AUS, 1/7 (14%) of SLNBs were falsely negative. CONCLUSIONS: Our study is the first to specifically address the performance and utility of AUS/FNA and SLNB for MBC patients. AUS/FNA at diagnosis followed by SLN surgery provided accurate nodal staging and critical prognostic information to inform treatment recommendations. We recommend this approach for axillary management of MBC patients.