André Mattar

A case report of male breast cancer in a very young patient: What is changing?

Male breast cancer accounts for 1% of all breast cancer cases, and men tend to be diagnosed at an older age than women (mean age is about 67 years). Several risk factors have been identified, such as genetic and hormonal abnormalities.The present study reported the case of a 25-year-old man who was diagnosed with an advanced invasive ductal carcinoma; however, he did not have any important risk factors.Even though more data is emerging about this disease, more efforts to understand risk factors, treatment options and survival benefits are needed. In this case, we discussed the risk factors as well as the impaired fertility associated with breast cancer therapies.

A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisas approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®).

Abstract P6-02-06: Safety and feasibility of neoadjuvant combined chemotherapy of breast cancer with paclitaxel carried in a lipid nanoemulsion (LDE) associated with adriamycin and cyclophosphamide

Background The introduction of neoadjuvant chemotherapy considerably changed the natural history of breast cancer by permitting a big tumors to be operable, permitting less aggressive surgical procedures and when achieving complete pathological response prolonging the disease-free period. However, the chemotherapy schemes bear high toxicity rates and are even life-threatening. Neoadjuvant chemotherapy aims at reducing mortality and improving surgical options and offers an in vivo chemosensitivity testing at the same time. It is the ideal setting for clinical and translational research. Compared to the classical adjuvant treatment, it offers several advantages. Methods We performed a pilot study to evaluate the safety and feasibility of neoadjuvant combined chemotherapy of breast cancer with paclitaxel carried in a lipid nanoemulsion (LDE) associated with adriamycin and cyclophosphamide in comparison to the classical neoadjuvant chemotherapy paclitaxel, adriamicyn and cyclofosfamide (TAC). All the patients were women with recently diagnosed breast cancer who needed primary chemotherapy as the first treatment selected from Perola Byington Hospital in Sao Paulo - Brazil. Results From April 2006 to June 2008, 39 patients from a center for breast disorders (Perola Byington Hospital) were included in the study. These patients were randomized to the standard chemotherapy scheme (control arm – n=16) or LDE-paclitaxel (LDE arm – N=17). Six patients were excluded from the study because they did not complete at least 5 cycles of chemotherapy. We also excluded three patients because of lack of follow up. The majority of patients had stage III (37% IIIA and 27% IIIB). There was no significant difference among the groups, considering the clinical variables, so the sample was considered homogeneous. The patients were grouped in four different groups regarding the expression of ER, PR and CerbB2: Luminal subtype, Triple Negative, Her2-positive and Hybrid Luminal. We observed 37,5% of complete response in the control arm and 23,5% in the LDE arm. The partial response were 43,7% in the control group and 58,8% in the LDE group. The toxicity particularly in grade 3 and 4 events were substantially lower in LDE group: Nausea 11% vs 2,2%; Vomiting 7,3% vs 0.7% and neutropenia 8,8% vs 2,2%. Conclusion LDE scheme was effective and had lower grad 3 and 4 events than the TAC regiment. More studies are necessary to evaluate this approach. Citation Format: Andre Mattar, Luciana B Ferreira, Luiz H Gebrim, Roberto Hegg, Raul C Maranhao. Safety and feasibility of neoadjuvant combined chemotherapy of breast cancer with paclitaxel carried in a lipid nanoemulsion (LDE) associated with adriamycin and cyclophosphamide [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-02-06.

Abstract P2-05-17: Correlation between cyclin D1, estrogen and progesterone receptors in invasive breast cancer after short-term treatment with tamoxifen or anastrozole

INTRODUCTION: Hormone therapy is associated with reduced breast cancer mortality. The use of biomarkers that are predictive of early cellular responses has been explored as a predictor of hormone resistance. Estrogen and progesterone receptor positivity and cyclin D1 have been associated with resistance to treatment with tamoxifen. OBJECTIVES: The aim of this study was to investigate the variations in the levels of cyclin D1 and the estrogen and progesterone receptors (ER and PR, respectively) in postmenopausal patients with ER− or PR-positive breast cancer after short-term treatment (26 days) with tamoxifen, anastrozole or a placebo. METHODS: This was a prospective, randomized double-blind study conducted in 71 patients with infiltrating ductal carcinoma (stages II and III) receiving care at either Perola Byington Hospital or Sao Paulo Hospital (Sao Paulo, Brazil). The patients were divided into three groups based on their treatment during the preoperative period (26 days): P (placebo, N = 26), T (tamoxifen, 20 mg/day, N = 22) and A (anastrozole, 1 mg/day, N = 23). The biopsies were performed at diagnosis and after mastectomy (26th day), and the tumors were isolated by tissue microarray. Immunohistochemistry was performed using anti-cyclin D1 (Novocastra DCS-6), anti-ER (Dako-M7047) and anti-PR (Dako-M3569) antibodies. The semiquantitative analyses were performed using Allred criteria, and the statistical analyses were performed with the ANOVA parametric test (p ≤ 0.05). RESULTS: A reduction in the mean PR level from 4.22 (pre-treatment) to 1.94 (post-treatment) was observed only in patients treated with anastrozole (p = 0.01). A positive linear correlation between cyclin D1 and PR levels was observed in group A (p = 0.0001), whereas group T exhibited a negative correlation (p = 0.0001). No correlation was observed in group P (p = 0.35). CONCLUSION: PR and cyclin D1 are likely predictive of an early response to aromatase inhibitors in breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-17.

Anastrozole Reduces Progesterone and Proliferation Index in Short Term Hormone Therapy. A Prospective Placebo Double Blind Study.

Background: Identification of new biomarkers with potential predictive and prognostic role has contributed unequivocally to breast cancer treatment. Although traditionally endocrine therapy is based on Hormonal receptors status (estrogen - ER and progesterone- PR), some patients become hormone resistant. In order to identify a possible profile associated to hormonal resistance, some biomarkers have been assessed after short period primary hormone therapy (HT).Objectives: To compare the expression of Ki-67, Bcl2, Bax, Bak, ER and e PR in postmenopausal women with ER positive invasive ductal carcinomas (IDC), prior and after tamoxifen and anastrozole in neoadjuvant treatment.Methods: Fifty-eight patients with palpable ER-positive IDC (stage II and III) were double-blind randomized in a prospective placebo controlled study with three neoadjuvant HT groups for twenty-six days prior to surgical treatment: Anastrozole 1mg/day (n= 18), Placebo (n=25) and Tamoxifen 20mg/day (n= 15). Pre and post HT samples were disposed in tissue micro array blocks and submitted to immunohistochemical essay. Biomarkers status (Ki-67, Bcl2, Bax, Bak, ER and e PR) were obtained comparing each immunohistochemical evaluation of pre and post-surgery samples using semi-quantitative Allred9s method. Statistical analysis were performed using the GEE (General Estimation Equations) and Anova tests with significant p ≤ 0,05.Results: ER and PR status did not change significantly in placebo group (96% -96% and 76-72%) and KI-67 index variation was 40 to 52% (p>0,05), as expected. In Tamoxifen group, ER status was also stable during treatment (100-100%). However, in anastrozole group, ER status -originally 100% - lowered to 89%,(p>0,05) and also PR expression rates lowered significantly from 56% to 28% in post treatment (p=0,0007). Anastrozole group also showed a significant reduction in KI-67 status from 78% in the pre-treatment KI-67 to 39% in post treatment samples (p=0,0079). Tamoxifen group showed a slight increase of PR expression from 73% to 93% along a non-statistical significant variation of KI-67 status 67% pre-treatment to 47% post-treatment. The other biomarkers (RE, Bak, Bax, Bcl-2 )did not show any variation in the three groups evaluated.Conclusions: a significant reduction of PR and ki-67 status was associated to Anastrozol treatment (26 days, 1mg/day). Short primary HT was not associated to any variation in apoptosis-related proteins (Bak, Bax, Bcl-2) regardless the drug used. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2145.