Hieken, Tina J.

e19061 Background: Sentinel lymph node (SLN) biopsy for thin melanoma remains controversial. While most patients diagnosed with thin melanoma have an excellent prognosis, ~5% will die of their disease. With the growing number of thin melanomas, nearly 25% of all melanoma-related deaths now result from thin primary tumors. Yet these patients are unlikely to have LN disease at presentation and when SLN disease is identified, it is often minimal. It remains unclear whether SLN biopsy with selective LN dissection (LND) represents an opportunity to cure patients with high-risk thin melanoma or whether they are a subgroup with disease likely confined to the SLN(s) or of unclear clinical significance. We undertook this study to examine outcomes in patients with thin melanomas (<1.0mm on biopsy) who underwent SLN biopsy. Methods: From our Melanoma Registry, we identified 338 consecutive thin melanoma cases in 300 patients. Data were verified by pathology and record review. Median patient follow up was 61 months. SAS software was used for statistical analysis. Results: 36 of 300 patients (12%) underwent SLN biopsy. Patients selected for SLN biopsy were younger (median 58 v 69 yrs, p=0.03), their melanomas were thicker (median 0.9 v 0.25 mm), more often level IV/V (44 v 5%), ulcerated (11 v 0.3%) and 53 v 22% had ≥1 mitoses/mm2, all p<0.001. Two (5.5%) were SLN+, one with isolated tumor cells in a solitary SLN, the other with 2.0 and 0.2 mm foci in 2 of 2 SLNs. Neither had additional disease identified after LND. Recurrent disease developed in 6/36 SLN patients (16.7%) and in 20/264 non-SLN patients (6.6%), after a median 32 of months. Isolated regional recurrence as site of first relapse occurred in 9/264 non-SLN patients (3.4%) and in no patients after SLN biopsy, p<0.001. Disease-free and overall survival were governed by tumor thickness. Conclusions: SLN biopsy with selective LND provides excellent regional control and prognostic information for selected patients with thin cutaneous melanoma, and may alter treatment and improve outcome for patients who harbor LN disease. Pending ongoing randomized controlled trial results, selective completion LND for patients with thin melanoma and evidence of SLN metastases appears warranted.

PURPOSE Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)–positive DCIS. PATIENTS AND METHODS A phase II single-arm multicenter cooperative-group trial was conducted in postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery. Breast magnetic resonance imaging (MRI) was obtained at baseline, 3 months, and 6 months. The primary end point was change in 6-month MRI enhancement volume compared with baseline. RESULTS Overall, 79 patients were enrolled and 70 completed 6 months of letrozole. Of these, 67 patients had MRI data available for each timepoint. Baseline MRI volumes ranged from 0.004 to 26.3 cm 3 . Median reductions from baseline MRI volume (1.4 cm 3 ) were 0.6 cm 3 (61.0%) at 3 months ( P < .001) and 0.8 cm 3 (71.7%) at 6 months ( P < .001). Consistent reductions were seen in median baseline ER H-score (228; median reduction, 15.0; P = .005), progesterone receptor H-score (15; median reduction, 85.0; P < .001), and Ki67 score (12%; median reduction, 6.3%; P = .007). Of the 59 patients who underwent surgery per study protocol, persistent DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%). CONCLUSIONS In a cohort of postmenopausal women with ER-positive DCIS, preoperative letrozole resulted in significant imaging and biomarker changes. These findings support future trials of extended endocrine therapy as primary nonoperative treatment of some DCIS.

Background: A female survival advantage in cutaneous melanoma has been long recognized. However, whether this extends across all age groups, with risk stratification using the latest prognostic staging system or in the current era of efficacious systemic therapies is unknown. Therefore, we evaluated whether sex-based differences in melanoma survival persisted within a recent population-based patient cohort with consideration of these factors. Materials and Methods: We identified stage II−IV cutaneous melanoma patients from 2010 to 2014 Surveillance, Epidemiology, and End Results cancer registries data. We recalculated stage per American Joint Committee on Cancer 8th edition guidelines. Cancer-specific survival (CSS) was estimated by using the Kaplan–Meier method and multivariable Cox proportional hazards regression. Results: Of 16,807 patients (39.8% female), 8,990 were stage II, 4,826 stage III, and 2,991 stage IV at diagnosis. Unadjusted 3-/5-year CSS estimates for females versus males were 64.2% versus 59.7%, and 53.5% versus 49.9%, respectively, p ≤ 0.0001. Five-year CSS varied within each stage and across age strata of <45, 45 − 59, and ≥60 years. Within each stage, females <45 had better CSS than all other sex/age groups ( p < 0.0001). In multivariable analysis of stage II/III patients, female sex, younger age, and lower mitotic index retained favorable CSS prognostic significance ( p < 0.001). Conclusions: Sex-based differences in melanoma survival persist in a contemporary patient cohort staged with the latest prognostic system. These data may guide decision marking regarding adjuvant therapy, highlight the importance of including sex as a pre-specified clinical trial variable, and suggest that investigation of underlying biologic mechanisms may drive discovery of biomarkers and therapeutic targets to improve patient care.

Abstract Background Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort. Methods Patients with non-metastatic IBC treated in 2010–2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−), ER−/HER2− and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ2 tests were used to compare pCR rates, and Kaplan–Meier curves and Cox proportional hazards regression to analyse overall survival. Results Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2− in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER−/HER2− in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2− (6·2 per cent), HER2+ (38·8 per cent), ER−/HER2− (19·1 per cent) (P &lt; 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2− 64·9 per cent, HER2+ 74·0 per cent, ER−/HER2− 44·0 per cent; P &lt; 0·001) and by pCR within subtypes (all P &lt; 0·001). In multivariable analysis, ER−/HER2− subtype (hazard ratio 2·89 versus HER2+ as reference; P &lt; 0·001) and absence of total pCR (hazard ratio 3·23; P &lt; 0·001) predicted worse survival. Conclusion Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease.

Background Implant-based breast reconstruction (IBR) accounts for 70% of postmastectomy reconstructions in the United States. Improving the quality of surgical care in IBR patients through accurate measurements of outcomes is necessary. The purpose of this study is to compare the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data from our institution to our complete institutional health records database. Methods Data were collected and recorded for all patients undergoing IBR at our institution from 2015 to 2017. The data were completely identified and compared with our institutional NSQIP database for demographics and complications. Results The electronic health records data search identified 768 IBR patients in 3 years and NSQIP reported on 229 (30%) patients. Demographics were reported similarly among the 2 databases. Rates of tissue expander/implant infections (5.9% vs 1.8%; P = 0.003) and wound dehiscence (3.5% vs 0.4%; P = 0.003) were not reported similarly between our database and NSQIP. However, the rates of hematoma (2.7% vs 1.8%) and skin flap necrosis (2.5% vs 1.8%) were comparable between the two databases. In our database, 43% of all complications presented after 30 days of surgery, beyond NSQIP's capture period. Conclusions Databases built on partial sampling, such as the NSQIP, may be useful for demographic analyses, but fall short of providing data for complications after IBR, such as infections and wound dehiscence. These results highlight the utility and importance of complete databases. National comparisons of clinical outcomes for IBR should be interpreted with caution when using partial databases.

Abstract Breast cancer survivorship guidelines recommend at least annual follow-up visits, yet the degree to which this occurs in clinical practice is uncertain. Claims data from a US commercial insurance database (OptumLabs) were used to identify women treated with curative intent surgery for newly diagnosed breast cancer between 2006 and 2014. In 25 035 women, median follow-up was 3 years. In the second year after surgery, 9.6% of the patients did not visit a primary care provider, an oncologist, or a surgeon (guideline-nonadherent). The guideline-nonadherent proportion increased from 7.8% in women diagnosed in 2006 to 12.2% in those diagnosed in 2014 (two-sided Wald P &lt; .001). During years 2–6, guideline-nonadherence was also associated with older age, nonwhite race, no radiation, no chemotherapy, no endocrine therapy, and increasing time after surgery. There is a substantial and increasing rate of inadequate follow-up among breast cancer survivors. This has the potential to impair outcomes.

Background Male breast cancer (MBC) is a rare disease for which there is limited understanding of treatment patterns and prognostic factors. Methods Men with TNM stage I to stage III breast cancer diagnosed between 2004 and 2014 in the National Cancer Data Base were included. Trends in treatment modalities were described using the average annual percentage change (AAPC) and estimated using Joinpoint software for the analysis of trends. Kaplan‐Meier curves and the multivariate Cox proportional hazards regression model were used to compare survival between subgroups and to identify prognostic factors. Results A total of 10,873 MBC cases were included, with a median age at diagnosis of 64 years. Breast‐conserving surgery was performed in 24% of patients, and 70% of patients undergoing breast conservation received radiotherapy. Approximately 44% of patients received chemotherapy, and 62% of patients with estrogen receptor–positive disease received endocrine therapy. Oncotype DX was ordered in 35% of patients with lymph node–negative, estrogen receptor–positive/human epidermal growth factor receptor 2 (HER2)‐negative tumors. During the study period, there was a significant increase in the rates of total mastectomy, contralateral prophylactic mastectomy, radiotherapy after breast conservation, ordering of Oncotype DX, and the use of endocrine therapy ( P < .05). On multivariate analysis, factors found to be associated with worse overall survival were older age, black race, higher Charlson Comorbidity Index, high tumor grade and stage of disease, and undergoing total mastectomy. Residing in a higher income area; having progesterone receptor–positive tumors; and receipt of chemotherapy, radiotherapy, and endocrine therapy were associated with better overall survival. Conclusions Despite the lack of prospective randomized trials in patients with MBC, the results of the current study demonstrated that the treatment of this disease has evolved over the years. These findings further the understanding of the modern treatment and prognosis of MBC, and identify several areas for further research.

Background: Surgical-site infection after implant-based breast reconstruction adversely affects surgical outcomes and increases health care costs. This 11-year case-control study examines risk factors specific for surgical-site infection after immediate tissue expander/implant-based breast reconstruction. Methods: The authors performed a retrospective review to identify all consecutive patients with breast implant infections between 2006 and 2016. Patients who developed surgical-site infection after immediate tissue expander/implant-based breast reconstruction were included. Surgical-site infection was defined using the Centers for Disease Control and Prevention criteria; specifically, infections requiring hospital admission, intravenous antibiotics, or surgical intervention were included. The authors matched a control patient to each infection case by patient age and date of surgery. Patient demographics, medical comorbidities, and perioperative surgical variables were examined. Univariate and multivariable conditional logistic regression models were constructed. Results: A total of 270 breasts in 252 patients were evaluated. On multivariate analysis, patients with a higher body mass index (OR, 1.1 per 1 body mass index point increase; 95 percent CI, 1.0 to 1.2; p = 0.02), hypertension (OR, 6.5; 95 percent CI, 1.9 to 22.3; p = 0.002), neoadjuvant chemotherapy (OR, 2.6; 95 percent CI, 1.0 to 6.3; p = 0.04), axillary lymph node dissection (OR, 7.1; 95 percent CI, 1.7 to 29.2; p = 0.006), seroma formation (OR, 15.34; 95 percent CI, 3.7 to 62.5; p = 0.0001), and wound healing complications (OR, 23.91; 95 percent CI, 6.1 to 93.4; p < 0.0001) were significantly associated with surgical-site infection. Conclusions: Women with obesity, women with hypertension, and those treated with neoadjuvant chemotherapy are at increased risk of surgical-site infection. Further risks are also associated with postoperative seroma and wound complications. This may help patient selection and counseling, adjusted based on risk factors regarding complications of immediate implant-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.