MAX SENNA MANO
Projetos de Pesquisa
Unidades Organizacionais
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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- Return to work after breast cancer diagnosis: An observational prospective study in Brazil(2018) LANDEIRO, Luciana C. G.; GAGLIATO, Debora M.; FEDE, Angelo B.; FRAILE, Natalia M.; LOPEZ, Rossana M.; FONSECA, Leonardo G. da; PETRY, Vanessa; TESTA, Laura; HOFF, Paulo M.; MANO, Max S.Background In North America and Europe, return-to-work (RTW) rates vary among breast cancer (BC) survivors, from 24% to 66% and from 53% to 82% at 6 and 36 months after diagnosis, respectively. To date, there is a lack of data on RTW rates after BC diagnosis in Latin America. Therefore, the primary objectives of this study were to define RTW rates at 12 and 24 months after BC diagnosis and to identify the factors associated with RTW in this population. Methods In total, 125 employed women from a single institution with newly diagnosed BC were interviewed by telephone at 6, 12, and 24 months after diagnosis. Those who had inoperable or metastatic disease were excluded. Results Overall, RTW rates were 30.3% and 60.4% at 12 and 24 months after BC diagnosis, respectively. Most women reported that they received support from their employer, but only 29.1% reported having been offered work adjustments. In multivariate analysis, the factors associated with positive RTW outcomes included higher household income (odds ratio [OR], 17.76; 95% confidence interval [CI], 3.33-94.75; P = .001), breast-conserving surgery (OR, 9.77; 95% CI, 2.03-47.05; P = .004), and work adjustments (OR, 37.62; 95% CI, 2.03-47.05; P = .004). The factors associated with negative RTW outcomes included adjuvant endocrine therapy (OR, 0.11; 95% CI, 0.02-0.74; P = .023), and depression diagnosed after BC (OR, 0.07; 95% CI, 0.01-0.63; P = .017). Conclusions RTW rates in the current study were lower than those observed in developed countries but similar to the rates among low-income Americans. Workplace adjustments, higher income, breast-conserving surgery, endocrine therapy, and depression after BC played an important role in the RTW decision. Cancer 2018;124:4700-4710. (C) 2018 American Cancer Society.
conferenceObject CARDIAC SAFETY OF (NEO) ADJUVANT TRASTUZUMAB IN THE BRAZILIAN COMMUNITY SETTING: A SINGLE CENTER EXPERIENCE(2012) FONSECA, L. G.; TAKAHASHI, T. K.; MAK, M. P.; BARROSO-SOUSA, R.; TESTA, L.; HELENA, V. Petry; COSTA, R. De Paula; HOFF, P. M.; MANO, M. S.Background Trastuzumab-associated cardiotoxicity (TAC) has been established in the context of clinical trials. However, when newly registered agents are used in a broader patient population, their safety profile does not always mirror that of the pivotal trials. Trastuzumab (T) only became available in the Brazilian public sector in 2008 and herein we report our off-trial experience so far. Methods Retrospective, single center cohort of HER-2 positive breast cancer patients (pts) treated with (neo)adjuvant chemotherapy and T from July 2008 to March 2012. 95.3% were treated according to local protocol (11.4% TCH; 83.9% AC-TH). Major cardiac event (MCE) was defined as a left ventricular ejection fraction (LVEF) drop of 10% and absolute drop to < 50 % by echocardiogram (ECHO) or as symptomatic heart failure (HF) regardless of the LVEF value or any cardiac event considered clinically meaningful. A multivariable Cox proportional hazards model was used to control for other cardiac risk factors. Results 237 women were identified: median age 53 y (27-83), 99.6% ECOG-PS 0-1, median body mass index 27.4 kg/m2 (17 – 46), 30.4% had hypertension (HTN), 8.8% had diabetes mellitus (DM), 5.9% had previous cardiopathy. 54.8% had ER-positive tumors; 40.7% received neoadjuvant T; most were stage II or III (22.3% and 37.1%). Median number of ECHO assessments was 2.7 (0-6); 136 pts (57.2%) completed T as planned. 20.2% had MCE (13.9% discontinued T). 3.8% discontinued T due to symptomatic HF and 5% for non-cardiac reasons. 41.6% of MCE pts recovered cardiac function. Median initial LVEF was 64.83 ± 1.5 % (no event) vs 64.81 ± 1.5 % (MCE) p = 0.26; median 3-month LFVE was 64.67 ± 4 % (no event) vs 56.12 ± 3 % (MCE) p = 0.0036. HTN, DM, obesity, age, radiotherapy, use of anthracycline and previous cardiopathy were not significantly associated with TAC. Conclusions Our results suggest that TAC in our routine practice is slightly higher than reported in literature (6 to 17%), possibly reflecting selection bias in clinical trials. Symptomatic TAC was as expected for AC-TH (4%). We failed to identify risk factors for TAC, possibly due to the low number of events. Cardiac function must be closely monitored during T treatment and careful pt selection is crucial.- Serum levels of VEGF and MCSF in HER2+/HER2- breast cancer patients with metronomic neoadjuvant chemotherapy(2018) ARAI, Roberto J.; PETRY, Vanessa; HOFF, Paulo M.; MANO, Max S.Metronomic therapy has been gaining importance in the neoadjuvant setting of breast cancer treatment. Its clinical benefits may involve antiangiogenic machinery. Cancer cells induce angiogenesis to support tumor growth by secreting factors, such as vascular endothelial growth factor (VEGF). In breast cancer, Trastuzumab (TZM) based treatment is of key importance and is believed to reduce diameter and volume of blood vessels as well as vascular permeability. Here in we investigated serum levels of angiogenic factors VEGF and MCSF in patients receiving metronomic neoadjuvant therapy with or without TZM. We observed in HER2+ cohort stable levels of MCSF through treatment, whereas VEGF trend was of decreasing levels. In HER2- cohort we observed increasing levels of MCSF and VEGF trend. Overall, HER2+ patients had better pathological response to treatment. These findings suggest that angiogenic pathway may be involved in TZM anti-tumoral effect in the neoadjuvant setting.
- Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+and HER2-locally advanced breast cancer(2015) PETRY, V.; GAGLIATO, D. M.; LEAL, A. I. C.; ARAI, R. J.; LONGO, E.; ANDRADE, F.; RICCI, M. D.; PIATO, J. R.; BARROSO-SOUSA, R.; HOFF, P. M.; MANO, M. S.Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2-(TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m(2) during 8 weeks followed by weekly doxorubicin at 24 mg/m(2) for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.
conferenceObject Feasibility of two schedules of weekly paclitaxel as (neo)adjuvant treatment for patients (PTS) with HER2-negative breast cancer (BC) in the Brazilian community setting(2012) SANTANA, Iuri Amorim; OLIVEIRA, Julia Andrade De; AMARAL, Alan Alves; TESTA, Laura; LANDEIRO, Luciana Garcia; COSTA, Romulo Leopoldo de Paula; HAJIME, Marcelo; FERRARI, Marcela Simonis Martins; PETRY, Vanessa; COHN, Daniela J. B. Heinemann; HOFF, Paulo M.; MANO, Max S.conferenceObject Metronomic chemotherapy (MC) in the neoadjuvant setting: Results of two parallel feasibility trials in patients (pts) with HER2 positive (HER2+) and negative (HER2-) locally advanced breast cancer (LABC) (Traq-Me and TAME)(2012) PETRY, Vanessa; LEAL, Alessandro; ARAI, Roberto J.; MARINHO, Simone; PAIVA, Marcelo; PIATO, Jose R.; ROSA, Marcio; HOFF, Paulo M.; MANO, Max S.conferenceObject Metronomic chemotherapy (MC): Results of two feasibility trials in patients (pts) with HER2 positive (HER2+) and negative (HER2-) locally advanced breast cancer (LABC)(2012) PETRY, Vanessa; LEAL, Alessandro; ARAI, Roberto J.; PIATO, Jose R.; ANDRADE, Felipe; PAIVA, Marcelo; FERRAZ, Marcio R.; MARINHO, Simone; HOFF, Paulo Marcelo; MANO, Max S.Background: In SWOG0012, MC improved pathologic complete response (pCR) compared to standard neoadjuvant chemotherapy (NC). We evaluated the feasibility of MC with a taxane->anthracycline schedule, which has also been shown potentially superior to the inverse sequence. We also evaluated the feasibility of MC in combination with trastuzumab. Methods: The primary objective was feasibility (defined as a febrile neutropenia (FN) rate ≤10%). Secondary objectives were cardiac safety, tolerability and efficacy as measured by objective response and pCR. The original accrual goal was 25 Her2+ pts and 40 Her2- pts. Her2- pts received paclitaxel (100mg/m2) x8 weeks followed by doxorubicin (24mg/m2) x9 weeks combined with oral cyclophosphamide (100mg/day), without G-CSF. Her2+ pts also received weekly trastuzumab (4 mg/kg followed by 2mg/kg) concurrently with the entire CT. Results: Most pts were stage III (Her+: 8/9; Her-: 4/11). The Her2+ cohort was prematurely closed after 2(22%) pts developed G3 pneumonitis (both during the MC phase). Both recovered completely. There was 1 case of asymptomatic LVEF drop to below 50% (during the taxane phase); 1 pt had G2 hand-foot skin reaction (HFS) and another had G2 mucositis. The Her2- cohort was also prematurely closed with only 11 pts due to high rates of mucocutaneous toxicity (G3 HFS in 36%, G3 rash in 9%) and also because of SWOG0221 negative results. There were 2(18%) cases of FN, but no cases of pneumonitis. 1/11(9%) Her2- and 5/9(55%) Her2 + pts had a pCR. VEGF-related biomarkers were collected and will be presented at a later date. Conclusions: The proposed MC schedules proved too toxic to be considered for further clinical development. In addition, MC resulted in unexpectedly high rates of severe pulmonary toxicity when given in combination with trastuzumab. Her2+ but not Her2- pts had an impressively high pCR rate.- Cardiac Safety of (Neo)Adjuvant Trastuzumab in the Community Setting: A Single-Center Experience(2014) FONSECA, Leonardo Gomes da; GAGLIATO, Debora de Melo; TAKAHASHI, Tiago K.; MAK, Milena Perez; BARROSO-SOUSA, Romualdo; TESTA, Laura; HELENA, Vanessa Petry; COSTA, Romulo de Paula; HOFF, Paulo M.; MANO, Max S.Background: Trastuzunnab improves the survival of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). The incidence and long-term impact of trastuzumab-related cardiotoxicity in the community setting is of great clinical importance. Material and Methods: Patients with HER2-positive BC treated with (neo)adjuvant trastuzumab were retrospectively evaluated. Cardiotoxicity was defined as cardiac death or absolute decrease in left ventricular ejection fraction of at least 10% to a value less than 50%, or symptomatic heart failure. Results: We evaluated 237 patients: median age 53 years (range 27-83 years). 40.5% of these patients had received neoadjuvant and 59.5% adjuvant chemotherapy. The majority (83.9%) were treated with an anthracycline-based regimen. Median exposure to trastuzumab was 8 months (range 2-12 months). Cardiotoxicity was diagnosed in 20.2%, but symptoms only occurred in 3.8%. 41.6% recovered cardiac function. None of the risk factors were associated with cardiotoxicity. Conclusion: The incidence of trastuzumab-related cardiotoxicity found in this study was slightly higher than those reported in randomized clinical trials. Nevertheless, most patients were asymptomatic. We describe the cardiac outcomes of a non-selected population, which possibly reflects those found in the 'real world'. The risks versus benefits of trastuzumab use remain in favor of treatment, but cardiotoxicity should be monitored.
- Return to work after breast cancer diagnosis: An observational prospective study of 125 patients in South America(2017) LANDEIRO, L. G.; FRAILE, N. M. P.; FEDE, A. B.; FONSECA, L. G.; TESTA, L.; PETRY, V.; GONCALVES, M. S.; COSTA, R. D. P.; COHN, D. B.; FERRARI, M. M.; SUNAHARA, R. S.; GOUVEIA, A. C. C. de; MANO, M. S.