MAX SENNA MANO
Projetos de Pesquisa
Unidades Organizacionais
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
7 resultados
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- Neoadjuvant endocrine therapy in breast cancer: current role and future perspectives(2016) BARROSO-SOUSA, Romualdo; SILVA, Danilo D. A. Fonseca Reis; ALESSI, Joao Victor Machado; MANO, Max SennaLuminal breast cancer, as defined by oestrogen and/or progesterone expression by immunohistochemistry, accounts for up to 75% of all breast cancers. In this population, endocrine therapy is likely to account for most of the gains obtained with the administration of adjuvant systemic treatment. The role of adjuvant chemotherapy in these patients remains debatable since it is known that only a small fraction of patients will derive meaningful benefit from this treatment whilst the majority will be exposed to significant and unnecessary chemotherapy-related toxicities, in particular the elderly and frail. Therefore, neoadjuvant endocrine therapy (NET) becomes an attractive option for selected patients with hormonal-receptor positive locally advanced breast cancer. In this review, we discuss the current role of NET and future perspectives in the field.
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.- Biological therapies in breast cancer: Common toxicities and management strategies(2013) BARROSO-SOUSA, Romualdo; SANTANA, Iuri A.; TESTA, Laura; GAGLIATO, Debora de Melo; MANO, Max S.In recent years, a number of new molecules e commonly known as biological therapies e have been approved or are in late stages of regulatory evaluation for the treatment of advanced breast cancer. These innovative compounds have improved treatment efficacy and have probably contributed to the increase in survival length observed in some breast cancer subtypes. However, these agents are not deprived of toxicity, which can impair quality of life and may occasionally be life-threatening. In this article, we reviewed the most common toxicities associated with these drugs and provided a number of practical recommendations on their optimal clinical management.
- 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 Correlation between body mass index and pathologic complete response after neoadjuvant chemotherapy for locally advanced breast cancer(2015) LIMA, J. M. Silva; MATUTINO, A.; SILVA, S. Brito; SILVA-JUNIOR, A. A.; BOAS, M. Vilas; STEPHAN, B. Oliveira; VAIRSBERG, V. Van; PEREIRA, A. A. Lima; BARROSO-SOUSA, R.; MANO, M. Senna- 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.
conferenceObject Neoadjuvant chemotherapy for elderly breast cancer patients(2015) MATUTINO, A. Reis Brandao; LIMA, J. M. Silva; SILVA, S. Brito; BOAS, M. Vilas; STEPHAN, B. Oliveira; VAIRSBERG, V. Van; FRAILE, N. Moreno Perez; BARROSO-SOUSA, R.; MANO, M. Senna