The Role of Mastectomy in De Novo Stage IV Inflammatory Breast Cancer.

INTRODUCTION: The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population. METHODS: Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007-2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local-regional recurrence patterns were described and survival analyses were conducted. RESULTS: All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2-]: 31.1% vs. 44.2%; HR-negative [HR-]/HER2+: 24.4% vs. 15.4%; and HR-/HER2-: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p < 0.001). Of the 47 patients who completed trimodality therapy, 6 (12.8%) had a local-regional recurrence. Median overall survival (OS) was 19 months in the non-MRM group and 58 months in the MRM group (p < 0.001). On multivariable analysis, clinical N3 disease (hazard ratio 2.16, 95% confidence interval [CI] 1.07-4.37; p = 0.03) as well as tumor subtypes HR+/HER2- (hazard ratio 4.98, 95% CI 1.15-21.47; p = 0.03) and HR-/HER2- (hazard ratio 7.18, 95% CI 1.66-31.07; p = 0.008) were associated with decreased OS. Partial/complete response of distant disease to chemotherapy (hazard ratio 0.43, 95% CI 0.24-0.77; p = 0.005) and receipt of MRM (hazard ratio 0.52, 95% CI 0.29-0.93; p = 0.03) were independently associated with improved OS. CONCLUSIONS: In our retrospective study, MRM in de novo stage IV IBC patients is an independent factor associated with improved OS. Our findings strongly support the need for prospective randomized trials evaluating possible survival benefits of MRM in de novo stage IV IBC patients.

Secondary Angiosarcoma With C-MYC Amplification Following Prophylactic Bilateral Mastectomy and Autologous Breast Reconstruction: Report of a Case and Review of the Literature.

In this article, we report a very rare case of secondary angiosarcoma in a young woman with no prior history of breast cancer who had bilateral prophylactic mastectomies with autologous reconstruction due to a strong family history of breast cancer and BRCA1 gene variant of uncertain significance. The surgery was complicated by recurrent fat necrosis requiring several excisions and additional reconstruction followed by the development of localized lymphedema and subsequent angiosarcoma in the reconstructed breast 10 years later. The angiosarcoma was high grade with prominent epithelioid features associated with abundant tumor-infiltrating lymphocytes. Amplification of C-MYC locus 8q21.24 was demonstrated by fluorescence in situ hybridization study. We postulate that chronic trauma from several surgeries including tissue hypoxia and impaired lymphatic drainage may have provided a milieu for angiogenesis and mutagenic transformation. Amplification of C-MYC locus 8q21.24 was most likely a strong oncogenic driver of angiosarcoma. To the best of our knowledge, this is the first report of its kind in the literature.

Clinicopathological Features and Outcomes in Individuals with Breast Cancer and ATM, CHEK2, or PALB2 Mutations.

INTRODUCTION: The moderate-penetrance germline mutations ATM, CHEK2, and PALB2 are implicated in an increased risk of the development of breast cancer. Whether these mutations provide clinical utility to guide treatment strategies and prognosis remains unknown. METHODS: A retrospective case-control study from a tertiary institution compared patients with stage 0-III breast cancer, and positive for ATM, CHEK2, or PALB2 mutations, with a matched cohort selected by randomization and negative for mutations. Data acquisition included demographics, histopathologic, treatment, and clinical outcome variables. RESULTS: A total of 145 patients with breast cancer (144 female and 1 male) were analyzed-74 mutation-positive patients (24 ATM, 26 CHEK2, 24 PALB2) and 71 mutation-negative patients. Mutation-positive patients compared with mutation-negative patients had increased family history of breast cancer (79.7 vs. 52.9%, p < 0.001) and tumor size > 2.0 cm (63.1% vs. 42.3%, p = 0.015). Patients with prior knowledge of mutational status were more likely to proceed with total mastectomy and prophylactic mastectomy (74.5% vs. 25.5%, p < 0.02; and 65.5% vs. 34.5%, p < 0.001, respectively). The unadjusted recurrence rate was higher in mutation-positive patients compared with mutation-negative patients (24.3 vs. 8.5%, p = 0.01), although mutation status was not predictive for recurrence in Cox regression analysis. CONCLUSIONS: Patients positive for ATM, CHEK2, or PALB2 mutations had increased tumor size and were more likely to undergo extensive surgeries. Mutation status was not predictive of recurrence, although this lack of effect may have been mitigated by lower rates of recurrence in those who pursued total mastectomy. Further studies are needed to confirm these findings.

Differences in Re-excision Rates for Breast-Conserving Surgery Using Intraoperative 2D Versus 3D Tomosynthesis Specimen Radiograph.

BACKGROUND: Intraoperative specimen radiographs performed during breast conservation surgery for cancer reduces the need for re-excision for positive margins. We studied 2D versus 3D image-guided cavity margin excision and compared it to final pathology and need for additional surgery. METHODS: We conducted a retrospective review of 657 breast-conserving operations performed for cancer from 2013 to 2018. Procedures were performed by four surgeons at a single tertiary institution with access intraoperatively to 2D and 3D radiographs. Data collected included demographics, intraoperative margin assessment, final pathology, and re-excision rates. RESULTS: A total of 466 patients had 2D and 191 had 3D specimen imaging. The 2D group had a lower mean age and a higher body mass index and proportion of minority patients than the 3D group (P < 0.01). In the 3D group, there was a higher percentage of patients with mammographically denser breasts (P < 0.06); 58% of patients in the 3D group had additional imaging-directed cavity margins excised versus 32% of patients in the 2D group (P < 0.01). In the 2D group, 44 patients (9%) had positive final margins versus 8 patients (4%) in the 3D group (P = 0.02). No difference was found on total volume of excision (P = 0.56). The re-excision rate for the 2D group was 11% versus 5% for the 3D group (P = 0.02; adjusted odds ratio = 0.41, 95% confidence interval 0.19-0.86). CONCLUSIONS: Re-excision rates using both modalities are low. A lower re-excision rate is independently associated with 3D tomosynthesis. This allows surgeons to excise additional margins at the index operation, decreasing reoperations and anxiety/costs for patients.

Mammographic density changes in surgical weight loss-an indication for personalized screening.

BACKGROUND: Obesity and high radiologic breast density independently increase breast cancer risk. We evaluated the effect of surgical weight loss on mammographic density (MD). METHODS: Patients undergoing bariatric surgery and screening mammography (MG) were identified, data regarding demographics, comorbidities, calculated and genetic breast cancer risk was collected. Patients had a MG before and after surgery. Fellowship-trained breast radiologists assigned Breast Imaging Reporting and Data System density categories. RESULTS: Patients underwent sleeve gastrectomy (n = 56) or gastric bypass (n = 7), 78% had hypertension, 48% had diabetes. Four had deleterious BRCA mutations, four were calculated high risk. Mean weight loss = 28.7 kg. Mean initial BMI = 44.3 kg/m2 (range:33-77), final BMI = 33.6 kg/m2 (range:20-62;p < 0.01). Density was unchanged in 53, decreased in 1, increased in 9. Of these 9(14%), 5 changed from almost entirely fatty to scattered MD, and 4 changed from scattered MD to heterogeneously dense. Mean weight loss of the 9 with increased MD was greater than the cohort (37.7vs.28.7 kg;p < 0.01). CONCLUSIONS: Surgical weight loss increased MD in 14%. Increased MD masks malignancies, patients may benefit from additional screening based on calculated risk assessments that include MD.

Characterizing End-of-Life Care after Geriatric Burns at a Verified Level I Burn Center.

BACKGROUND: End-of-life (EoL) care after geriatric burns (geri-burns) is understudied. OBJECTIVE: To examine the practices of burn surgeons for initiating EoL discussions and the impact of decisions made on the courses of geri-burn patients who died after injury. METHODS: This retrospective cohort study examined all subjects ≥65 years who died on our Level I burn service from April 1, 2009, to December 31, 2014. Measurements obtained were timing of first EoL discussion (EARLY <24 hours post-admission; LATE ≥24 hours post-admission), decisions made, age, total body surface area burned, and calculated probability of death at admission. RESULTS: The cohort consisted of 57 subjects, of whom 54 had at least one documented EoL care discussion between a burn physician and the patient/surrogate. No differences were seen between groups for the likelihood of an immediate decision for comfort care after the first discussion (p = 0.73) or the mean number of total discussions (p = 0.07). EARLY group subjects (n = 38) had significantly greater magnitudes of injury (p = 0.002), calculated probabilities of death at admission (p ≤ 0.001), shorter times to death (p ≤ 0.001), and fewer trips to the operating theater for burn excision and skin grafting (p ≤ 0.001) than LATE subjects (n = 16). LATE subjects' first discussion occurred at a mean of 9.3 ± 10.0 days. DISCUSSION: The vast majority of geri-burn deaths on our burn service occur after a discussion about EoL care. The timing of these discussions is driven by magnitude of injury, and it does not lead to higher proportions of an immediate decision for comfort care. The presence and timing of EoL discussions bears further study as a quality metric for geri-burn EoL care.