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.

Prognostic Predictors of Mortality in Male Breast Cancer: Outcomes in an Urban Population.

INTRODUCTION: Male breast cancer (MBC) accounts for 0.5% to 1% of all breast cancers diagnosed annually. The purpose of this study is to evaluate prognostic factors in MBC. METHODS: We performed a retrospective chart review of patients with MBC between 2010 and 2021. Demographics, comorbidities, cancer characteristics, recurrence, and mortality were collected. Cox proportional hazards regression model was used to determine prognostic factors. A Kaplan-Meier curve was used to plot survival probabilities. RESULTS: A total of 47 male patients were identified. The mean age at presentation was 64.1 y. Twenty eight (59.6%) patients were African American and 14 patients (29.8%) were Caucasian. Most patients had invasive ductal carcinoma (89.4%) and presented with T1 or T2 tumors (40.4% and 38.3%, respectively). Three patients (6.4%) had a recurrence and eight patients (17%) died. Using mortality as an end point, age (≥ 76.1 y) indicated a hazard ratio (HR) of 1.13 (P = 0.004), diabetes mellitus (HR = 5.45, P = 0.023), atrial fibrillation (HR = 8.0, P = 0.009), end-stage renal disease (HR 6.47, P = 0.023), Eastern Cooperative Oncology Group performance status of 3 (HR = 7.92, P = 0.024), poorly differentiated grade (HR = 7.21, P = 0.033), and metastatic disease (HR = 30.94, P = 0.015) had an increased risk of mortality. Overall survival at 3 y was 79.2%. CONCLUSIONS: Advanced age, diabetes mellitus, atrial fibrillation, end-stage renal disease, Eastern Cooperative Oncology Group score of 3, poorly differentiated tumors, and metastatic disease are unfavorable prognostic factors in MBC. Compared to female breast cancer, MBC showed poorer overall survival.

A retrospective cohort study comparing reconstructive techniques and outcomes in post-mastectomy triple negative breast cancer patients.

Background: Up to 42% of all breast cancer patients undergo post-mastectomy reconstruction, however reconstructive techniques have not been widely studied in patients with triple negative breast cancer (TNBC). Reconstructive complications may delay adjuvant treatments; in TNBC, which inherently carries an increased risk of locoregional recurrence, this can greatly affect oncological outcomes. Therefore, we evaluate factors influencing choice of reconstructive techniques following mastectomy in TNBC patients and assess operative and oncologic safety outcomes. Methods: A single institution retrospective chart review identified TNBC patients who underwent post-mastectomy reconstruction between 2010 to 2020. Clinical characteristics collected included demographics, cancer history, reconstructive techniques [autologous-based reconstruction (ABR) vs. implant-based reconstruction (IBR)] and surgical and oncologic outcomes such as complications, recurrence, and mortality. Factors impacting whether patients underwent ABR versus IBR were assessed, as well as differences in outcomes between the two procedures. Statistical significance was defined as P<0.05. Results: During the 10-year period, 52.9% (n=127) of all post-mastectomy TNBC patients (n=240) underwent breast reconstruction, most frequently immediately after mastectomy (97.0%). Most patients underwent IBR compared to ABR (82.4% vs. 14.5%). Patients undergoing ABR were older than IBR patients (54.3 vs. 46.4 years; P=0.040) and had a higher body mass index (BMI; 30.0 vs. 26.1 kg/m2; P=0.007). Patients more often pursued ABR if they had a prior breast cancer history (36.8% vs. 16.7%; P=0.041) or experienced TNBC recurrence (26.3% vs. 9.3%; P=0.034), while primary TNBC patients more often opted for IBR. Reconstructive type did not impact complications (ABR 31.6% vs. IBR 16.8%, P=0.131), recurrence (ABR 15.8% vs. IBR 13.0%, P=0.719), or mortality (ABR 0.0% vs. IBR 6.5%, P=0.593) rates. Conclusions: Factors such as age, BMI, and breast cancer history impacted choice of reconstructive technique among TNBC women. No differences in complications, recurrence, or mortality occur in these high-risk patients regardless of reconstructive technique, highlighting that neither ABR nor IBR is superior in regard to surgical and oncologic safety in post-mastectomy TNBC patients.

Triple negative breast cancer and reconstruction: Predictors of recurrence, complications, and mortality.

BACKGROUND: Only 42% of all breast cancer patients undergoing mastectomy elect for breast reconstruction. OBJECTIVE: We evaluate factors impacting complications, recurrence, and mortality in triple-negative breast cancer (TNBC) patients undergoing reconstruction. METHODS: Reconstructive TNBC patients at a single institution from 2010 to 2020 were retrospectively reviewed. Patient demographics, cancer characteristics, reconstruction choice, and complications were collected. Statistical significance was defined at p < 0.05. RESULTS: A total of 131 patients were identified. Average age was 47.8 years, 50.4% were Caucasian and 36.4% were African American. Most patients had invasive ductal carcinoma (90.8%), and most underwent nipple-sparing (41.2%) or skin-sparing (38.9%) mastectomies. Twenty-one patients (16.0%) experienced postoperative complications. Patients with complications tended to be older (52.1 versus 46.9 years, p = 0.052). At mean follow-up of 52.1 months, 14.5% experienced cancer recurrence and 5.3% died. Deceased patients were significantly younger at diagnosis (42.2 versus 48.5 years, p = 0.008) and had a lower BMI compared to surviving patients (21.2 versus 26.9 kg/m2; p = 0.014). Patients younger than age 45 years had higher Ki-67 than those older than 45 years (80.0% versus 60.0%, p = 0.013). Outcomes in autologous- versus implant-based reconstruction were not significantly different. CONCLUSIONS: In TNBC post-mastectomy reconstruction patients, age and BMI were predictors of mortality while race, smoking history, reconstruction choice, or type of implant-based reconstruction had no significant effect on these outcomes. SYNOPSIS: The purpose of this study is to evaluate factors that impact complications, recurrence, and mortality in triple negative breast cancer (TNBC) patients undergoing reconstruction. We identified BMI, neoadjuvant chemotherapy, and age as predictors of complications, recurrence, and mortality in TNBC.

Postmastectomy Reconstruction in Male Breast Cancer.

Introduction: Less than 1% of all breast cancers are diagnosed in males. In females, postmastectomy breast reconstruction is associated with increased patient satisfaction. However, there is a paucity of literature describing reconstructive options for postmastectomy deformity in the male chest. The purpose of this systematic review was to evaluate postmastectomy reconstruction outcomes in males with breast cancer. Methods: A systematic review was performed in accordance with PRISMA guidelines. Ovid MEDLINE, Embase, Cochrane, and Web of Science were queried for records pertaining to the study question using medical subject heading (MeSH) terms such as "male breast cancer," "mastectomy," and "reconstruction." No limitations were placed on the year of publication, country of origin, or study size. Study characteristics and patient demographics were collected. Primary outcomes of interest included postoperative complications, recurrence rate, and mortality rate. Results: A total of 11 articles examining 29 male patients with breast cancer who underwent postmastectomy reconstruction were included for analysis. Literature was most commonly available in the form of case reports. The average age was 59.6 +/-11.4 years. Reconstruction methods included fat grafting (n = 1, 3.4%), silicone implants (n = 1, 3.4%), and autologous chest wall reconstruction with local flaps (n = 26, 89.7%). Postoperative complications occurred in two patients (6.8%), including partial nipple necrosis (n = 1) and hypertrophic scarring (n = 1). Of the studies reporting patient satisfaction, all patients were pleased with the aesthetic appearance of their chest. Conclusion: This systematic review revealed the limited availability of research regarding postmastectomy chest reconstruction in males with breast cancer. Nevertheless, the evidence available suggests that reconstruction can restore a patient's body image and, thus, should be regularly considered and discussed with male patients. Larger studies are warranted to further shed light on this population.

Positive margins after mastectomy in patients with invasive lobular carcinoma of the breast: Incidence and management strategies.

BACKGROUND: Surgical treatment of invasive lobular carcinoma (ILC) is challenging due to its diffuse growth pattern, and the positive margin rate after mastectomy is poorly described. METHODS: We retrospectively determined the positive margin rate in those with stage I-III ILC undergoing mastectomy. We evaluated the relationship between management strategy and recurrence free survival (RFS). RESULTS: In 357 patients, the positive margin rate was 10.6% overall and 18.7% in those with T3 tumors. Having a positive margin was associated with significantly shorter RFS on multivariate analysis (p = 0.01). Undergoing additional local treatment (radiation or re-excision) for a positive margin was significantly associated with improved RFS (p = 0.004). Older women with positive margins were significantly less likely to undergo additional local therapy. CONCLUSIONS: Even mastectomy fails to clear margins in a high proportion of patients with large ILC tumors, a finding which may warrant testing neoadjuvant strategies even prior to planned mastectomy.

Treating Positive Axillary Disease in Elderly Breast Cancer Patients: The Impact of Age on Radiation Therapy.

INTRODUCTION: Breast cancer is the second most common cause of cancer death in females, and 30% of these patients are over the age of 70 years. Studies have shown deviation from the standard treatment paradigms in the elderly, especially in regard to radiation treatment. METHODS: We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital to examine which patient factors influenced radiotherapy. RESULTS: Increasing patient age was associated with a decrease in the probability of receiving radiotherapy, while HER2-negative patients were more likely to receive radiation. Neither race, number of coexisting medical conditions, or insurance status showed any influence on radiation treatment. CONCLUSION: Patient age has a significant influence if elderly patients with axillary disease receive radiotherapy. Further investigation and validation are needed to understand why chronological age rather than biological age influences treatment modalities.

Oncological Outcomes of Total Skin-Sparing Mastectomy for Invasive Lobular Carcinoma of the Breast: A 20-Year Institutional Experience.

BACKGROUND: Although rates of total skin-sparing (nipple-sparing) mastectomies are increasing, the oncologic safety of this procedure has not been evaluated in invasive lobular carcinoma (ILC). ILC is the second most common type of breast cancer, and its diffuse growth pattern and high positive margin rates potentially increase the risk of poor outcomes from less extensive surgical resection. METHODS: We compared time to local recurrence and positive margin rates in a cohort of 300 patients with ILC undergoing either total skin-sparing mastectomy (TSSM), skin-sparing mastectomy, or simple mastectomy between the years 2000-2020. Data were obtained from a prospectively maintained institutional database and were analyzed by using univariate statistics, the log-rank test, and multivariate Cox proportional hazards models. RESULTS: Of 300 cases, mastectomy type was TSSM in 119 (39.7%), skin-sparing mastectomy in 52 (17.3%), and simple mastectomy in 129 (43%). The rate of TSSM increased significantly with time (p < 0.001) and was associated with younger age at diagnosis (p = 0.0007). There was no difference in time to local recurrence on univariate and multivariate analysis, nor difference in positive margin rates by mastectomy type. Factors significantly associated with shorter local recurrence-free survival were higher tumor stage and tumor grade. CONCLUSIONS: TSSM can be safely offered to patients with ILC, despite the diffuse growth pattern seen in this tumor type.

Obesity Does Not Influence Management of Advanced Breast Cancer in the Elderly.

BACKGROUND: Obesity is becoming increasingly common in the elderly population, and it adds to the complexity of treatment decisions in this population. We aimed to investigate whether body mass index (BMI) affects care in this subset of patients. PATIENTS AND METHODS: We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital and compared BMI to treatment received, clinical stage, and hormone receptor status. RESULTS: Performance of radiation therapy, axillary surgery, and chemotherapy was compared in the elderly population over lower and higher BMI, and no significant difference was detected. Although there was a trend for increasing clinical stage to be associated with a lower BMI, this was not statistically significant (P = .06). CONCLUSION: Obesity does not appear to influence treatment decisions in patients over the age of 70 years. Breast cancer providers should turn to other patient and clinical factors when deciding treatment plans in this patient population. Further investigation is needed to examine how obesity influences tumor biology, diagnosis, and treatment decisions.

Marjolin's Ulcer in Chronic Hidradenitis Suppurativa: A Rare Complication of an Often Neglected Disease.

Hidradenitis suppurativa (HS) is a chronic, debilitating disease with definitive treatment consisting of wide surgical excision of all affected tissue. Originally described in burns, Marjolin's ulcer (MU) has been described in a variety of wound types, including hidradenitis. HS patients often have long delays to diagnosis and management of their chronic wounds, leading to increased risk of MU. A retrospective review of our burn database was performed from 2008 to 2014. Seventy-two consecutive patients taken to the operating room for HS were retrospectively evaluated for demographic data, number of excisions, total area of excised skin, need for skin grafting, pathology results, and outcome. Fifty-eight percent of patients were male. Mean age was 36.88 ± 13.52 years. Mean size of excision was 743.71 ± 774.75 cm. Total number of operative procedures was 187, averaging 2.612 per patient, with 52% of patients undergoing skin grafting. Two patients had confirmed pathology of squamous cell carcinoma. Both were women with perineal HS and had metastatic disease on further workup. Both patients underwent chemotherapy and radiation with progression of their disease. The incidence of MU of 2.78% in this study is similar to the 2% incidence described historically in the burn population. All practitioners who treat HS patients should be aware of the devastating complication of MU arising in the chronic wound bed. We recommend that all excised tissue be sent to pathology for evaluation, and to consider early wide local excision of any chronically inflamed tissues to alleviate the risk of MU for this patient population.

Non-enzymatically derived minor lipids found in Escherichia coli lipid extracts.

Electrospray ionization mass spectrometry is a powerful technique to analyze lipid extracts especially for the identification of new lipid metabolites. A hurdle to lipid identification is the presence of solvent contaminants that hinder the identification of low abundance species or covalently modify abundant lipid species. We have identified several non-enzymatically derived minor lipid species in lipid extracts of Escherichia coli; phosphatidylmethanol, ethyl and methyl carbamates of PE and N-succinyl PE were identified in lipid extracts of E. coli. Phosphatidylmethanol (PM) was identified by exact mass measurement and collision induced dissociation tandem mass spectrometry (MS/MS). Extraction in the presence of deuterated methanol leads to a 3 atomic mass unit shift in the [M-H](-) ions of PM indicating its formation during extraction. Ethyl and methyl carbamates of PE, also identified by exact mass measurement and MS/MS, are likely to be formed by phosgene, a breakdown product of chloroform. Addition of phosgene to extractions containing synthetic PE significantly increases the levels of PE-MC detected in the lipid extracts by ESI-MS. Extraction in the presence of methylene chloride significantly reduced the levels of these lipid species. N-succinyl PE is formed from reaction of succinyl-CoA with PE during extraction. Interestingly N-succinyl PE can be formed in an aqueous reaction mixture in the absence of added E. coli proteins. This work highlights the reactivity of the amine of PE and emphasizes that careful extraction controls are required to ensure that new minor lipid species identified using mass spectrometry are indeed endogenous lipid metabolites.

Identification of phosphatidylserylglutamate: a novel minor lipid in Escherichia coli.

Advances in mass spectrometry have facilitated the identification of novel lipid structures. In this work, we fractionated the lipids of Escherichia coli B and analyzed the fractions using negative-ion electrospray ionization mass spectrometry to reveal unknown lipid structures. Analysis of a fraction eluting with high salt from DEAE cellulose revealed a series of ions not corresponding to any of the known lipids of E. coli. The ions, with m/z 861.5, 875.5, 887.5, 889.5, and 915.5, were analyzed using collision-induced dissociation mass spectrometry (MS/MS) and yielded related fragmentation patterns consistent with a novel diacylated glycerophospholipid. Product ions arising by neutral loss of 216 mass units were observed with all of the unknowns. A corresponding negative product ion was also observed at m/z 215.0. Additional ions at m/z 197.0, 171.0, 146.0, and 128.0 were used to propose the novel structure phosphatidylserylglutamate (PSE). The hypothesized structure was confirmed by comparison with the MS/MS spectrum of a synthetic standard. Normal phase liquid chromatography-mass spectrometry analysis further showed that the endogenous PSE and synthetic PSE eluted with the same retention times. PSE was also observed in the equivalent anion exchange fractions of total lipids extracted from the wild-type E. coli K-12 strain MG1655.