PIK3CA mutations in Peruvian patients with HER[2]-amplified and triple negative non-metastatic breast cancers

To determine the frequency of PIK3CA mutations in a Peruvian cohort with HER2-amplified and triple negative breast cancers [TNBC]. We analyzed two cohorts of 134 primary non-metastatic breast cancer patients from Peru. Cohorts consisted of 51 hormone receptors [+]/HER2-amplified breast tumor patients surgically resected as first treatment included in the ALTTO trial [ALTTO cohort] and 81 TNBC patients with residual disease after neoadjuvant treatment [neoadjuvant cohort]. Genomic DNA was extracted from paraffin-embedded tumor samples. Samples from the ALTTO and neoadjuvant cohorts were taken at biopsies and from residual tumors, respectively. PIK3CA mutations were detected by sequencing DNA fragments obtained by PCR amplification of exons and their flanking introns. All of the detected PIK3CA mutations were confirmed in a second independent run of sample testing. PIK3CA mutations were present in 21/134 cases [15.7%]. Mutations in exon 9 and 20 were present in 10/134 [7.5%] and 11/134 [8.2%], respectively. No cases had mutations in both exons. Mutations in exon 9 consisted of E545A [seven cases], E545K [two cases] and E545Q [one case]; while in exon 20, mutations consisted of H1047R [10 cases] and H1047L [one case]. Compared to TNBC patients, HER2-amplified patients were more likely to have PIK3CA mutated [23% vs 9.6%; P = 0.034]. There were no associations between mutational status of PIK3CA with estrogen receptor status [P = 0.731], progesterone receptor status [P = 0.921], age [P = 0.646], nodal status [P = 0.240] or histological grade [P = 1.00]. No significant associations were found between PIK3CA mutational status and clinicopathological features. We found a similar frequency of PIK3CA mutations to that reported in other series. Although we did not include HR+/HER2 patients, those with HER2-amplified tumors were more likely to present PIK3CA mutations compared to patients with triple negative tumors

Addition of amifostine to the CHOP regimen in elderly patients with aggressive non-Hodgkin lymphoma: a phase II trial showing reduction in toxicity without altering long-term survival

We report the 8-year follow-up of 34 patients aged >/= 69 years old with NHL included in a phase IIb open-label randomized parallel groups study to evaluate the effectiveness of amifostine in preventing the toxicity of cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP regime]. Patients were randomized to receive classical CHOP [cyclophosphamide 750 mg/ m[2], doxorubicin 50 mg/m[2], vincristine 1.4 mg/m[2] [maximum 2 mg] on day 1 and prednisone 100 mg/day for 5 days] or CHOP plus amifostine [6 cycles of amifostine 910 mg/m[2] on day 1]. Efficacy [time to progression, TTP; disease-free survival, DFS; overall survival, OS] and toxicity endpoints were evaluated. Thirty-four patients were randomized to A-CHOP [n=18] or CHOP [n=16]. Patients with A-CHOP vs CHOP had significantly lower toxicity; neutropenia grade 4 ocurred in 13/92 [13%] vs 23/85 [27%, P=0.007] cycles, febrile neutropenia in 3/92 A-CHOP [3%] vs 8/85 [10%, P=.056] CHOP cycles, hospitalization for toxicity in 4/92 [4%] A-CHOP vs 11/85 [13%, P=.05] CHOP cycles. Median hospitalization stay for toxicity was 5 days with A-CHOP vs 8 days with CHOP [P=.05]. There were no significant differences at 8 years in TTP [A-CHOP, 48.9% vs CHOP, 36.3%; P=.65], DFS [A-CHOP, 72.9% vs CHOP 55.6%; P=.50] and OS [A-CHOP, 44.3% vs CHOP, 54.4%]. There was no long-term toxicity of clinical interest. The only prognostic factor identified to 8 years was the International Prognostic Index [IPI low/low intermediate risk vs high intermediate/high risk; HR=2.98; CI 95%:1.01-8.77; P=.048]. These results show that amifostine can be added to the standard CHOP treatment schedule with less acute toxicity and without influencing the outcome

Prognostic effect of hormone receptor status in early HER2 positive breast cancer patients

This study was conducted to determine the prognostic effect hormone receptor [HR] status in early HER2 positive [HER2+] breast cancer patients, since it has not yet been established whether HR status can be used in the prognosis of patients with [HER2+] breast cancer. We obtained data from 299 patients with early HER2+ breast cancer who underwent surgery and received standard adjuvant chemotherapy, hormonal therapy and/or radiation between 2000 and 2002 at the Instituto Nacional de Enfermedaldes Neoplasticas, Peru. Clinical and pathological features were compared. Endpoints analyzed were disease free survival [DFS] and overall survival [OS]. Overall, 155 patients were HR-positive [HR+] and 144 were negative [HR-]. The two groups had similar characteristics except for histologic grade and extracapsular extension. With a median follow-up of 93 months, 5-year DFS was statistically different between the two groups: 65.0% for [HER2+/HR-] and 74.6% for the [HER2+/HR+] patients [P=.045]. OS at 5 years was not statistically different between the two groups with 75.5% for [HER2+/HR-] patients and 82.4% for the [HER2+/HR+] [P=.140]. Patients with [HER2+/HR-] breast cancers treated with surgery and standard adjuvant chemotherapy exhibited a statistically worse DFS compared to those with [HER2+/HR+] tumors. However, OS was similar in both groups