Racial-ethnic variations in phyllodes tumors among a multicenter United States cohort.

BACKGROUND AND OBJECTIVES: Previous studies have identified racial-ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial-ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT. METHODS: We performed an 11-institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence-free survival according to race-ethnicity. RESULTS: Women of non-White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non-Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence-free survival in our cohort. CONCLUSIONS: Differences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race-ethnicity. These conclusions are supported by our finding that there were no differences in recurrence-free survival.

Immediate Lymphatic Reconstruction after Axillary Lymphadenectomy: A Single-Institution Early Experience.

PURPOSE: Lymphedema is progressive arm swelling from lymphatic dysfunction which can occur in 30% patients undergoing axillary dissection/radiation for breast cancer. Immediate lymphatic reconstruction (ILR) is performed in an attempt decrease the risk of lymphedema in patients undergoing axillary lymph node dissection (ALND). The purpose of this study was to assess the efficacy of ILR in preventing lymphedema rates in ALND patients. METHODS: An institutional review board-approved retrospective review was performed of all patients who underwent ILR from 2017 to 2019. Patient demographics, comorbidities, operative and pathologic findings, number of LVAs, limb measurements, complications, and follow-up were recorded and analyzed. Student's sample t-test, Fisher's exact test, and ANOVA were used to analyze data; significance was set at p < 0.05. RESULTS: Thirty-three patients were included in this analysis. Three patients (9.1%) developed persistent lymphedema, and two patients (6.1%) developed transient arm edema that resolved with compression and massage therapy. A significant effect was found for body mass index and the number of lymph nodes taken on the development of lymphedema (p < 0.01). CONCLUSIONS: The rate of lymphedema in this series was 9.1%, which is an improvement from historical rates of lymphedema. Our findings support ILR as a technique that potentially decreases the incidence of lymphedema after axillary lymphadenectomy. Obesity and number of lymph nodes removed were significant predictive variables for the development of lymphedema following LVA.

Limited Reporting of Histopathologic Details in a Multi-Institutional Academic Cohort of Phyllodes Tumors: Time for Standardization.

BACKGROUND: Phyllodes tumors are rare fibroepithelial neoplasms that are classified by tiered histopathologic features. While there are protocols for the reporting of cancer specimens, no standardized reporting protocol exists for phyllodes. METHODS: We performed an 11-institution contemporary review of phyllodes tumors. Granular histopathologic details were recorded, including the features specifically considered for phyllodes grade classification. RESULTS: Of 550 patients, median tumor size was 3.0 cm, 68.9% (n = 379) of tumors were benign, 19.6% (n = 108) were borderline, and 10.5% (n = 58) were malignant. All cases reported the final tumor size and grade classification. Complete pathologic reporting of all histopathologic features was present in 15.3% (n = 84) of cases, while an additional 35.6% (n = 196) were missing only one or two features in the report. Individual details regarding the degree of stromal cellularity was not reported in 53.5% (n = 294) of cases, degree of stromal atypia in 58.0% (n = 319) of cases, presence of stromal overgrowth in 56.2% (n = 309) of cases, stromal cell mitoses in 37.5% (n = 206) of cases, and tumor border in 54.2% (n = 298) of cases. The final margin status (negative vs. positive) was omitted in only 0.9% of cases, and the final negative margin width was specifically reported in 73.8% of cases. Reporting of details was similar across all sites. CONCLUSION: In this academic cohort of phyllodes tumors, one or more histopathologic features were frequently omitted from the pathology report. While all features were considered by the pathologist for grading, this limited reporting reflects a lack of reporting consensus. We recommend that standardized reporting in the form of a synoptic-style cancer protocol be implemented for phyllodes tumors, similar to other rare tumors.

Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing.

BACKGROUND: A paucity of data exists regarding inherited mutations associated with phyllodes tumors (PT); however, some are reported (TP53, BRCA1, and RB1). A PT diagnosis does not meet NCCN criteria for testing, including within Li-Fraumeni Syndrome (TP53). We sought to determine the prevalence of mutations associated with PT. METHODS: We performed an 11-institution review of contemporary (2007-2017) PT practice. We recorded multigenerational family history and personal history of genetic testing. We identified patients meeting NCCN criteria for genetic evaluation. Logistic regression estimated the association of select covariates with likelihood of undergoing genetic testing. RESULTS: Of 550 PT patients, 59.8% (n = 329) had a close family history of cancer, and 34.0% (n = 112) had ≥ 3 family members affected. Only 6.2% (n = 34) underwent genetic testing, 38.2% (n = 13) of whom had only BRCA1/BRCA2 tested. Of 34 patients tested, 8.8% had a deleterious mutation (1 BRCA1, 2 TP53), and 5.9% had a BRCA2 VUS. Of women who had TP53 testing (N = 21), 9.5% had a mutation. Selection for testing was not associated with age (odds ratio [OR] 1.01, p = 0.55) or PT size (p = 0.12) but was associated with grade (malignant vs. benign: OR 9.17, 95% CI 3.97-21.18) and meeting NCCN criteria (OR 3.43, 95% confidence interval 1.70-6.94). Notably, an additional 86 (15.6%) patients met NCCN criteria but had no genetic testing. CONCLUSIONS: Very few women with PT undergo germline testing; however, in those selected for testing, a deleterious mutation was identified in ~ 10%. Multigene testing of a PT cohort would present an opportunity to discover the true incidence of germline mutations in PT patients.

The Role of the Surgeon in the Germline Testing of the Newly Diagnosed Breast Cancer Patient.

For patients with newly diagnosed breast cancer, information regarding hereditary predisposition can influence treatment decisions. From a surgical standpoint, patients with known germline mutations may alter decisions of local therapy to reduce the risk of second breast primaries. This information may also be considered in the choice of adjuvant therapies or eligibility for clinical trials. In recent years, the criteria for the consideration of germline testing in patients with breast cancer has expanded. Additionally, studies have shown a similar prevalence of pathogenic mutations in those patients outside of these traditional criteria, prompting calls for genetic testing for all patients with a history of breast cancer. While data confirms the benefit of counseling by certified genetics professionals, the capacity of genetic counselors may no longer meet the needs of these growing numbers of patients. National societies assert that counseling and testing can be performed by providers with training and experience in genetics. Breast surgeons are well positioned to offer this service, as they receive formal genetics training during their fellowship, manage these patients daily in their practices, and are often the first providers to see patients after their cancer diagnosis.

The no-vertical scar technique for oncoplastic breast reconstruction.

INTRODUCTION: Oncoplastic reconstruction can optimize breast conserving therapy. Nipple loss is a concern in patients with significant ptosis and breast hypertrophy particularly with pedicle undermining during tumor resection. The modified Robertson technique (No-Vertical Scar reduction) has been previously described for breast reduction in large, ptotic patients using a wide, bell-shaped inferior pedicle with only inframammary fold and peri­areolar incisions. The purpose of this study was to evaluate the No-Vertical Scar (NVS) technique applied to oncoplastic reconstruction. METHODS: Women undergoing oncoplastic breast reduction using a NVS, Wise, or Vertical method were assessed. Predictive variables included patient demographics, comorbidities, and sternal notch to nipple (SNN) distance. Outcome variables were delayed wound healing, surgical site infection, seroma, fat necrosis, nipple necrosis, use of a free nipple graft, and time between surgery and adjuvant radiation. RESULTS: Fifty patients met inclusion criteria using NVS (N = 15), Wise (N = 16), and Vertical (N = 19) methods. The NVS group had a significantly higher BMI (p=.009), greater sternal notch to nipple distance (p=<0.001) and increased resection volume (p=<0.001) as compared to Wise and Vertical groups. There was no significant difference in complications (p=.25). No nipple necrosis occurred, and no free nipple grafts were required. CONCLUSION: The NVS approach is a useful technique for oncoplastic reconstruction in select patients with macromastia and severe Grade II or Grade III ptosis. The wide, bell-shaped pedicle is versatile for obliterating a lumpectomy cavity and optimizing nipple perfusion if pedicle undermining occurs during resection.

Referral process to further evaluate poor sleep in breast cancer survivors.

OBJECTIVE: Breast cancer survivors (BCS) are twice as likely to report symptoms of poor sleep as those without cancer. However, sleep disorders are under-assessed and under-treated among BCS. The purpose of this study was to determine the portion of BCS who completed referral visits to a sleep specialist and identify the acceptability, facilitators, and barriers to the screening and referral process. METHODS: BCS, who reported having sleep problems, completed questionnaires to screen for symptoms suggestive of sleep disorders. Those with symptoms suggestive of sleep apnea, movement disorders, narcolepsy, insomnia syndrome, or circadian disorders, they were referred to a sleep medicine physician or behavioral sleep medicine psychologist. Two months after the referral, participants were interviewed about their perceptions of the acceptability, barriers, and facilitators to sleep screenings and referrals. RESULTS: Of 34 BCS assessed for eligibility, 29 were eligible and had sleep problems. Only eight of 29 participants (27.6%) completed the sleep referral process. Most thought the screening and referral process was acceptable. However, BCS identified barriers to completing the referral visit, including time, not seeing the need for treatment, insurance/sick leave concerns, and distance/transportation. CONCLUSION: Adequate evaluation and treatment of sleep disorders in BCS are rare. Creative solutions to address barriers to timely sleep referrals are needed to reduce long-term negative consequences of inadequate sleep.

Optimizing tissue expander breast reconstruction in nicotine users: An algorithmic approach.

INTRODUCTION: Smoking is a risk factor for post-operative complications following breast reconstruction. Abruptly refraining from all nicotine products may be difficult for patients with a new cancer diagnosis. The goal of this study is to assess complications following a distinct approach to tissue expander reconstruction in nicotine users. METHODS: Patients who underwent tissue expander reconstruction after mastectomy were retrospectively reviewed. The approach to optimize outcomes in smokers was to delay reconstruction at least 7 days after the mastectomy and place the expander submuscularly (Group I). The other patients underwent standard immediate reconstruction on the day of mastectomy and were divided into Group II (active smokers) and Group III (non-smokers). Group III was considered the control group. RESULTS: There was a total of 195 patients (323 breast reconstructions): Group I (10 patients, 19 expanders); Group II (11 patients, 19 expanders) and Group III (174 patients, 285 expanders). In Group I, n = 1/19 breasts had wound dehiscence requiring surgical management, compared to n = 18/285 in Group III (p = 1.0). Group II exhibited more wound dehiscence (n = 6/19) compared to Group III (p = 0.002). There was no significant difference when comparing wound dehiscence in prepectoral expander placement (7.0%) versus submuscular placement (4.8%) in Group III (p = 0.60). CONCLUSION: Nicotine users who are offered tissue expander breast reconstruction 1) at least 7 days after the mastectomy (to allow for vascular delay and demarcation) and 2) in the submuscular plane can normalize their risk of skin necrosis to that of non-smokers who have standard (prepectoral or submuscular) reconstruction on the day of mastectomy.

Contemporary Multi-Institutional Cohort of 550 Cases of Phyllodes Tumors (2007-2017) Demonstrates a Need for More Individualized Margin Guidelines.

PURPOSE: Phyllodes tumors (PTs) are rare breast neoplasms, which have little granular data on margins. Current guidelines recommend ≥ 1 cm margins; however, recent data suggest narrower margins are sufficient, and for benign PT, a negative margin may not be necessary. METHODS: We performed an 11-institution contemporary (2007-2017) review of PT practices. Demographics, surgical, and histopathologic data were captured. Logistic regression was used to estimate the association of select covariates with local recurrence (LR). RESULTS: Of 550 PT patients, the majority underwent excisional biopsy (55.3%, n = 302/546) or lumpectomy (wide excision) (38.5%, n = 210/546). Median tumor size was 30 mm, 68.9% (n = 379) were benign, 19.6% (n = 108) borderline, and 10.5% (n = 58) malignant. Surgical margins were positive in 42% (n = 231) and negative in 57.3% (n = 311). A second operation was performed in 38.0% (n = 209) of the total cohort, including 51 patients with an initial negative margin (82.4% with < 2 mm), and 157 with an initial positive margin, with residual disease only found in six (2.9%). Notably, 32.0% (n = 74) of those with an initial positive margin did not undergo a second operation, among whom only 2.7% (n = 2) recurred. Recurrence occurred in 3.3% (n = 18) of the total cohort (n = 15 LR, n = 3 distant), at median follow-up of 36.7 months. LR (all PT grades) was not reduced with wider negative margin width (≥ 2 mm v < 2 mm: odds ratio [OR] = 0.39; 95% CI, 0.07 to 2.10; P = .27) or final margin status (positive v negative: OR = 0.96; 95% CI, 0.26 to 3.52; P = .96). CONCLUSION: In current practice, many patients are managed outside of current guidelines. For the entire cohort, a wider margin width was not associated with a reduced risk of LR. We do not recommend re-excision of a negative margin for benign PT, regardless of margin width, as a progressively wider surgical margin is unlikely to reduce LR.

Breast Cancer Cell Detection and Characterization from Breast Milk-Derived Cells.

Radiologic techniques remain the main method for early detection for breast cancer and are critical to achieve a favorable outcome from cancer. However, more sensitive detection methods to complement radiologic techniques are needed to enhance early detection and treatment strategies. Using our recently established culturing method that allows propagation of normal and cancerous breast epithelial cells of luminal origin, flow cytometry characterization, and genomic sequencing, we show that cancer cells can be detected in breast milk. Cells derived from milk from the breast with cancer were enriched for CD49f+/EpCAM-, CD44+/CD24-, and CD271+ cancer stem-like cells (CSC). These CSCs carried mutations within the cytoplasmic retention domain of HDAC6, stop/gain insertion in MORF4L1, and deletion mutations within SWI/SNF complex component SMARCC2. CSCs were sensitive to HDAC6 inhibitors, BET bromodomain inhibitors, and EZH2 inhibitors, as mutations in SWI/SNF complex components are known to increase sensitivity to these drugs. Among cells derived from breast milk of additional ten women not known to have breast cancer, two of them contained cells that were enriched for the CSC phenotype and carried mutations in NF1 or KMT2D, which are frequently mutated in breast cancer. Breast milk-derived cells with NF1 mutations also carried copy-number variations in CDKN2C, PTEN, and REL genes. The approach described here may enable rapid cancer cell characterization including driver mutation detection and therapeutic screening for pregnancy/postpartum breast cancers. Furthermore, this method can be developed as a surveillance or early detection tool for women at high risk for developing breast cancer. SIGNIFICANCE: These findings describe how a simple method for characterization of cancer cells in pregnancy and postpartum breast cancer can be exploited as a surveillance tool for women at risk of developing breast cancer.

The implications of insurance status on presentation, surgical management, and mortality among nonmetastatic breast cancer patients in Indiana.

BACKGROUND: The National Breast and Cervical Cancer Early Detection Program seeks to reduce health care disparities by providing uninsured and underinsured women access to screening mammograms. The objective of this study is to identify the differences in presentation, surgical management, and mortality among nonmetastatic uninsured patients diagnosed through Indiana's Breast and Cervical Cancer Program compared with patients with private and government (Medicare or Medicaid) insurance. METHODS: Study data were obtained using the Indiana state cancer registry and Indiana's Breast and Cervical Cancer Program. Women aged 50 to 64 with an index diagnosis of stage 0 to III breast cancer from January 1, 2006 to December 31, 2013, were included in the study. Bivariate intergroup analysis was conducted. Kaplan-Meier estimates between insurance types were compared using the log rank test. All-cause mortality was evaluated using a mixed effects model. RESULTS: The groups differed significantly for sociodemographic and clinical variables. Uninsured Indiana Breast and Cervical Cancer Program patients presented with later disease stage (P < .001) and had the highest overall mortality (hazard ratio 2.2, P = .003). Surgical management only differed among stage III patients (P = .012). CONCLUSION: To improve insurance-based disparities in Indiana, implementation of the Breast and Cervical Cancer Program in conjunction with expansion of insurance coverage to vulnerable low-income populations need to be optimized.

Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review.

BACKGROUND: Mutations in BRCA1 or BRCA2 genes results in an elevated risk for developing both breast and ovarian cancers over the lifetime of affected carriers. General surgeons may be faced with questions about surgical risk reduction and survival benefit of prophylactic surgery. METHODS: A systematic literature review was performed using the electronic databases PubMed, OVID MEDLINE, and Scopus comparing prophylactic surgery vs observation with respect to breast and ovarian cancer risk reduction and mortality in BRCA mutation carriers. RESULTS: Bilateral risk-reducing mastectomy provides a 90% to 95% risk reduction in BRCA mutation carriers, although the data do not demonstrate improved mortality. The reduction in ovarian and breast cancer risks using risk-reducing bilateral salpingo-oophorectomy has translated to improvement in survival. CONCLUSIONS: Clinical management of patients at increased risk for breast cancer requires consideration of risk, patient preference, and quality of life.