The influence of breast cancer subtypes on the response to anthracycline neoadjuvant chemotherapy in locally advanced breast cancer patients.

PURPOSE: The objective of neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC) is downstaging to achieve resectability. According to the protocol for the treatment of LABC more than 10 years ago, the routine NACT for LABC in Serbia consisted of 4 cycles of FAC (fluorouracil, doxorubicin, cyclophosphamide). The aim of this analysis was to assess the influence of biologic subtypes of BC on the response to NACT and on the disease outcome in these patients. METHODS: We analyzed 190 patients with median age of 52 years (range 26-74), diagnosed with LABC between Jun/2002 and Dec/2005 and treated with 4 cycles of FAC. Patients with clinical response to NACT (162/192;85.26%) were subjected to radical mastectomy after which the majority of them received 3 cycles of adjuvant FAC, adjuvant tamoxifen if HR-positive disease, and postoperative radiotherapy. We retrospectively determined by immunohistochemistry estrogen receptor (ER)/ progesterone receptor (PgR)/HER2 status from BC biopsies in all patients who were divided in 4 subgroups. Pathological complete remission (pCR) was defined as ypT0N0. The main end points were disease-free survival (DFS) and overall survival (OS). Statistics included Fisher's exact test, KaplanMeier product-limit method and Log-rank test. RESULTS: After a median follow up of 76 months (range 3-128) 104/190 patients (54.74%) experienced disease relapse, while 78/190 (41.05%) died. Of 157 patients with known receptor status the numbers of 4 subtypes were as follows: 31/190 (16.32%) triple negative (TN) BC, 22/190 (11.58%) HR-/HER2+, 97/190 (51%) HR+/HER2- and 17/190 (8.95%) HR+/HER2+. Ten out of 190 patients (6.17%) achieved pCR and had significantly longer DFS (Log-rank test, p=0.042), and a trend to prolonged OS (Log-rank test, p=0.092). There was a significant difference (Fisher exact test, p=7.7 × 10-6) between pCR rates among 4 BC subtypes: 3/31 (9.68%) in TNBC, 6/22 (27.27%) in HR-/HER2+, 0/97 in HR+/HER2- and 1/17 (5.88%) in HR+/HER2+ patients. This difference was achieved on the account of the difference between TNBC and HR-/HER2+ BC subtypes (Fisher's exact test, p=6.85×10-6, Bonferroni correction: 0.05/6=0.0083). There were no differences in DFS and OS between the 4 BC subtypes. CONCLUSION: Although there was a significantly higher number of patients achieving pCR among HR-/HER2+ subtype compared to other BC subtypes, this did not translate into improvement in long-term disease outcome of these patients.

Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy: a single institution experience.

PURPOSE: The aim of this research was to examine overall (OS) and disease-free survival (DFS) in patients with colorectal peritoneal carcinomatosis (CRC-PC), treated with cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), as well as to analyse factors of prognostic significance. METHODS: We included 61 patients with pathological/and computerized tomography (CT) confirmation of CRC-PC, treated with CRS+HIPEC from 2005 to 2012. Peritoneal Cancer Index (PCI) score was used for quantitative assessment of the CRC-PC extent. We performed CRS following the Sugarbaker's principles in all patients with PCI ≤20 and only in 3/61 (4.92%) patients with PCI >20. HIPEC (oxaliplatin 410 mg/m(2) in 2000mL isotonic solution and 41?C) was performed using RanD Performer® HT perfusion system during 30-60 min. Cox proportional hazard regression was used to determine significant factors for OS and DFS. RESULTS: The follow-up ranged from 1 to 83 months (median 22). Median OS was 51 months (95% confidence interval/ CI 22+). Median DFS for patients without residual disease (57/61, 93.44%) was 23 months (95% CI 16+). One-, 2- and 6-year OS (DFS) were 78.6% (68.3%), 58.7% (46.7%) and 50.5% (38.1%), respectively. By the end of the study, 55.74% of the patients were still alive. Cox multivariate analysis indicated PCI score as a parameter of highly prognostic significance for patients treated with CRS+HIPEC (p<0.001). Patients with PCI (13 (vs PCI ≥13) had significantly longer OS and DFS (p<0.001), also confirmed for PCI subcategories (PCI <7 vs 7≤ PCI <13 vs PCI ≥13). All patients with PCI <7 are still alive. CONCLUSION: Our study indicates that CRS+HIPEC significantly improves the survival of CRC-PC patients. This treatment modality should be considered as the most suitable in well-selected patients with this disease.

Immunity to melanin and to tyrosinase in melanoma patients, and in people with vitiligo.

BACKGROUND: The aim of this study was to determine the presence and the intensity of humoral immunity to melanoma-associated antigens: tyrosinase and melanin, in patients with melanoma, in persons with vitiligo and in control healthy people. METHODS: The study involved 63 patients with melanoma and 19 persons with vitiligo. Control group consisted up to 41 healthy volunteers. Mushroom tyrosinase and synthetic melanin were used as the antigens. RESULTS: ELISA test showed significantly (p < 0.0000004 and p < 0.04) lower levels of IgM anti-tyrosinase autoantibodies, in melanoma and vitiligo patients respectively, compared to controls.Although there was no significant difference between the levels of IgA anti-melanin autoantibodies in melanoma or vitiligo patients in comparison with controls, the enhanced concentrations of anti-melanin IgA autoantibodies were preferentially found in melanoma patients with metastatic disease. Significantly high percentage in the Fc alphaRI (CD89) positive cells was determined in melanoma patients (p < 0.002 and p < 0.008) in comparison to that found in healthy people or in patients with vitiligo, in the already mentioned order, pointing that IgA dependent cellular cytotoxicity is not important for the immune action against melanoma, even more that it is included in some immune suppression.Levels of IgG autoantibodies to mentioned antigens in melanoma patients although low were not significantly lower from controls. These findings analyzed together with the statistically significant low percentage of FcgammaRIII, (CD16) positive immunocompetent cells (p < 0.0007 and p < 0.003), which was found in patients with melanoma compared with healthy or vitiligo people respectively, and statistically significant low percentage of (CD16 + CD56+) natural killer (NK) cells (p < 0.005) found in melanoma patients in comparison to healthy controls pointed to the low probability for anti-melanoma IgG mediated, antibody mediated cellular cytotoxicity, (ADCC) and NK cytotoxicity. Moreover the ratio of the percentages of granulocytes and percentage of lymphocytes was statistically higher in patients with melanoma in relation to healthy people as well as to people with vitiligo (p < 0.0007 and p < 0.05 respectively). CONCLUSION: Autoantibodies to tyrosinase and to melanin which are found even in healthy people, point that consummation of edible mushrooms that carry the antigen tyrosinase and melanin, could influence the humoral anti-melanoma immune response.Levels of different immunoglobulin classes of anti-melanin and anti-tyrosinase antibodies varied depending on the presence and the stage of studied diseases. Besides, the statistically enhanced ratio of the percentages of granulocytes and percentage of lymphocytes, together with statistically decreased percentage of NK cells is found in analyzed melanoma patients.