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Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy.HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model.Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r 0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale.Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes.ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91.

Microsatellitosis (mS) in melanoma has been considered a marker of unfavorable tumor biology, leading to the current American Joint Committee on Cancer staging of IIIB/C/D disease, despite few investigative studies of this entity limited by the small sample sizes and incomplete nodal microstaging. We sought to better characterize outcomes and prognostic factors in a multi-institutional cohort of patients with mS and nodal microstaging. The Sentinel Lymph Node Working Group cohort included 414 mS patients who underwent sentinel lymph node (SLN) biopsy. Cox regression analysis was used to evaluate the prognostic significance of established clinicopathologic characteristics. Melanoma-specific survival (MSS) of patients with mS was compared with 3002 similarly staged patients from the Surveillance, Epidemiology, and End Results (SEER) Program registry. The median age of the mS cohort was 64.9 years; 39.6% were female. Median thickness was 3 mm, 40.6% of cases were ulcerated, and the SLN positivity rate was 46.7%. Increasing thickness, male sex, and SLN positivity were significantly associated with poorer MSS. Stage IIIB/C/D 5-year MSS rates were 86.3% (95% confidence interval [CI] 79.4–93.3%), 54.1% (95% CI 45.4–59.7%), and 44.2% (95% CI 25.4–63.0%), respectively. MSS survival for the stage IIIB mS cohort was significantly better than a similarly staged SEER cohort (5-year MSS of 70.1%, 95% CI 66.0–74.2%), while no significant difference was observed for the stage IIIC or D cohorts. SLN metastases are common and are a significant prognostic factor in patients with mS. Survival in stage IIIB patients with mS was considerably more favorable than their stage would otherwise suggest, which has important implications for decisions regarding adjuvant therapy for patients with mS.

Controversy continues regarding the use of adjuvant radiation therapy (RT) and hormonal therapy (HT) for patients undergoing breast-conserving therapy (BCT) for ductal carcinoma in situ (DCIS). A prospective database was queried to identify women 18 years of age or older treated for DCIS from 2002 to 2013. BCT was completed for 300 patients with a median age of 66 years. The median DCIS size was 0.7 cm (range 0.1–6.0 cm). The DCIS grades were high (44 %), intermediate (37 %), and low (19 %). The closest margin was wider than 3 mm in 80 % and wider than 5 mm in 63 % of the cases. Adjuvant RT was administered to 183 patients (61 %), and the RT status of 9 patients (3 %) was unknown. RT was associated with age, DCIS size, comedo necrosis, grade, and treatment in 2002–2007 versus 2008–2013. Adjuvant HT was administered to 86 estrogen receptor-positive patients (39 %), and the HT status of 4 patients (2 %) was unknown. The median follow-up period was 63 months (range 4–151 months). The 5-year overall local recurrence (LR) rate was 4 % (95 % confidence interval [CI] 2.1–7.4 %). The 5-year LR rate was 3.9 % (95 % CI 1.8–8.6 %) for the RT patients and 4.1 % (95 % CI 1.6–10.7 %) for the patients not receiving RT. Of 13 LRs, 10 (77 %) were DCIS, and 3 (23 %) were invasive including one node-positive recurrence. Multidisciplinary and joint decision making in the treatment of DCIS results in a substantial and increasing number of patients forgoing adjuvant RT, adjuvant HT, or both. Reasonable 5-year LR rates suggest that such decision making can appropriately allocate patients to adjuvant therapies.

Proper patient selection is important for nipple-sparing mastectomy, and we aimed to identify preoperative factors predictive of pathologic nipple-areola complex (NAC) involvement to assist with surgical planning. We retrospectively reviewed a prospectively collected database of patients who underwent mastectomy for DCIS or invasive breast cancer at a single institution. Cases with NAC involvement, NAC(+), were compared with those without NAC involvement, NAC(−). Multivariate logistic regression analysis was performed to determine preoperative factors independently predictive of NAC involvement. A total of 238 standard, 107 skin-sparing, and 47 nipple-sparing mastectomies were performed, and the NAC was pathologically involved in 16% (N = 62). Clinical NAC involvement, as determined by patient symptoms or physical exam, was present in 61% of NAC(+) but only 14% of NAC(−) cases (P

Surgical therapy for invasive breast cancer includes breast conservation therapy (BCT), unilateral mastectomy (UM), or bilateral mastectomy, including contralateral prophylactic mastectomy (CPM) with or without reconstruction (±R). The goal of this study was to determine factors associated with CPM. A breast cancer database collected from 2000 through 2008 was retrospectively reviewed. Treatment groups analyzed included BCT, UM ± R, and CPM ± R. Variables were compared using ANOVA F-tests and chi-square tests. Multivariate analysis was performed using logistic regression. A total of 1,391 patients underwent surgery for invasive breast cancer: 69% BCT, 21% UM, and 10% bilateral mastectomy. Of those undergoing bilateral mastectomy, 30% had bilateral cancer and were excluded from analysis. The rate of CPM increased significantly from 0 to 20% (p

Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed. Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2−) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1–3 based on observed mitoses. A total of 1292 ER+, HER2− invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0–14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p

The significance of androgen receptor (AR) expression in triple-negative breast cancer (TNBC) is unclear, and published studies so far have been inconclusive.A tissue microarray was constructed using tissue obtained from 119 patients with primary TNBC and stained for AR expression. Other tissue types obtained included recurrent TNBC, normal breast tissue, adjacent ductal carcinoma-in situ (DCIS), lymph node (LN) and distant metastases. Positive AR expression was defined as ≥10% nuclear staining.Epithelial tissue was present and evaluable in 94 TNBC patients with a total of 177 tissue cores. AR expression in TNBC was 22 of 94 (23%). AR expression was higher in normal breast tissue (88%) and adjacent DCIS (73% overall). All LN metastases from AR-positive TNBC patients were also AR positive; in addition, no AR-negative TNBC patient had AR-positive LNs. AR expression was associated with older patient age (63 vs. 57 years, respectively, p = 0.051) and LN metastases (p = 0.033). Locoregional recurrence and overall/disease-specific survival were similar between AR-positive and AR-negative patients, although AR-positive patients had more advanced disease. On multivariate analysis, the presence of LN metastases was associated with poorer recurrence-free survival in AR-positive patients (hazard ratio, 4.34) (p = 0.031).The AR is expressed in normal breast tissue, and expression decreases with advancement to DCIS and invasive cancer. AR-positive TNBC was more common in older patients and had a higher propensity for LN metastases. AR-positive TNBC may represent a breast cancer subtype with unique features that may be amenable to treatment with alternative targeted therapies.

Obesity has been linked to many adverse health consequences, including breast cancer; however, the impact on clinical presentation, tumor characteristics, and survival outcomes has yet to be clearly defined.Retrospective review of a prospectively collected database of patients treated at a single institution for invasive breast cancer from 2000-2008 comparing two groups: nonobese (body mass index of30) and obese (body mass index of ≥ 30) patients. Continuous variables, categorical variables, and survival data were analyzed.Of 1352 total patients, 76% were classified as nonobese and 24% were obese. When comparing age, obese patients presented less frequently than nonobese patients50 years old (10% vs. 90%), and when comparing patients50 years old (18% vs. 82%, P = 0.0019). Obese patients were more likely to present with disease detected by imaging when compared to nonobese patients (67% vs. 56%, P = 0.0006). Obese patients had larger tumors (1.7 cm vs. 1.4 cm, P0.001) and higher rates of lymph node (LN) metastases (31% vs. 25%, P = 0.026). On multivariate analysis, obesity was associated with nonpalpable tumors, larger tumors, a higher incidence of LN metastasis, lower incidence of Her2 positivity, lower incidence of multifocality, and less likely to undergo reconstruction after mastectomy.Obese patients clinically present at older ages with mammographically detected breast cancer at more advanced stages than nonobese patients. Strategies to encourage screening among the obese patient population are important.

Breast cancer screening recommendations are in flux. We reviewed the methods of detecting newly diagnosed breast neoplasms at our institution. A retrospective review of patients stratified by age was performed to compare mammography with self- (SBE) and clinical (CBE) breast examination methods of cancer detection from 2005 to 2009. We identified 782 patients. Patients aged

Triple-negative (TN) breast cancers lack estrogen receptor (ER), progesterone receptor (PR), and HER2/neu amplification (HER2). Few studies have been dedicated to characterizing this subset of cancer. Retrospective review of a prospectively collected database of patients treated for invasive breast cancer at a single institution. Three tumor marker groups were compared: TN [ER−/PR−/HER2−], HER2+ [ERx/PRx/HER2+], and ER+ [ER+/PRx/HER2−]. Over 8 years, 123 TN, 210 HER2+, and 728 ER+ patients were identified. On average, TN patients were younger (mean age TN 59.7, HER2+ 62.0, ER+ 64.5 years, P = 0.0001). They were referred for genetic testing more frequently (17% TN, 10% HER2+, 10% ER+, P = 0.055) and were most likely to have a BRCA mutation identified if tested (24% TN, 10% HER2+, 4% ER+, P = 0.019). TN tumors were larger (mean size 2.1 cm TN, 2.0 cm HER2+, 1.8 cm ER+, P = 0.031) and most commonly detected by breast exam (54% TN, 43% HER2+, 42% ER+, P = 0.025). Lymph node involvement was least common with TN tumors (21% TN, 37% HER2+, 32% ER+, P = 0.013), and angiolymphatic invasion was less common for TN than HER2+ (18% TN, 24% HER2+, 15% ER+, P = 0.006). TN patients had significantly higher local or regional recurrence (5.7% TN, 2.9% HER2+, 1.0% ER+, P = 0.001), and the worst 5-year overall survival, although this did not reach statistical significance (85% ± 6% TN, 94% ± 2% HER2+, 91% ± 2% ER+). TN breast cancers are associated with unique patient presentations, tumor characteristics, and clinical outcomes of which clinicians and investigators should be aware.