This report is on a patient, who presented purpura and hemarthrosis in a context of vitamin C deficiency. This case gives us the opportunity to discuss the differential diagnosis, the clinical features, the pathogenicity and the treatment of this rare condition.

No abstract

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

PurposesMost molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.Patients and MethodsWe collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes.ResultsPAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors.ConclusionsThis is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America.Clinical Trial RegistrationClinicalTrials.gov (Identifier: NCT02326857).

The event-free survival (EFS) and overall survival (OS) were estimated by the KaplaneMeier method and compared between patients at different disease characteristics using the log-rank test. Results: There are total 3151 patients across 19 countries, including 200 patients in Taiwan subgroup. The EFS and OS of total population were 10.3 (interquartile range, 8.8 to 11.8) months and 24.8 (interquartile range, 21.3 to 27.4) months, respectively. The patients with stage IIIA and stage IIIB NSCLC have similar median EFS (11.4 vs. 9.2 months, respectively; P ¼ 0.143) and median OS (29.5 vs. 24.1 months, respectively; P ¼ 0.085). In contrast, patients with resectable disease have better median EFS (13.4 vs. 8.6 months, respectively; P ¼ 0.014) and OS (33.9 vs. 20.5 months, respectively; P < 0.001) than patients with unresectable disease. Moreover, in either resectable subgroup or unresectable subgroup, both the EFS and OS were also similar between patients with stage IIIA and IIIB NSCLC. These data indicate that the resectability is a more important prognostic factor than stage among patients with stage III NSCLC. Among 55 patients with resectable disease, 53 underwent the surgery and 2 received chemo-radiotherapy (CRT)-based therapy. The median EFS was significantly longer in patients undergoing the surgery compared to those receiving CRT-based therapy (14.7 vs. 7.5 months, respectively; P ¼ 0.028); however, the median OS was not significantly different between the two cohorts (34.9 vs. 25.5 months, respectively; P ¼ 0.339). Among 116 patients with unresectable disease, 38 received curative-intent CRT-based therapy and 78 received palliative therapy. Both median EFS and OS were comparable between patients receiving different treatment approaches. Conclusion: In the Taiwanese subgroup of KINDLE study, the resectability is the major prognostic factor in patients with stage III NSCLC. Although the surgery seemed to result in better EFS in patients with resectable disease, the OS was similar among patients receiving different treatment approaches. Further subgroup analysis is warranted to explore the predictive value of other baseline characteristics (e.g., TNM stage, EGFR status, subsequent therapy).