Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial.

Background: Denosumab is a fully human monoclonal antibody that binds to, and inhibits, the receptor activator of RANKL (TNFSF11) and might affect breast cancer biology, as shown by preclinical evidence. We aimed to assess whether denosumab combined with standard-of-care adjuvant or neoadjuvant systemic therapy and locoregional treatments would increase bone metastasis-free survival in women with breast cancer.

Method: In this international, double-blind, randomised, placebo-controlled, phase 3 study (D-CARE), patients were recruited from 389 centres in 39 countries.

Prevalence and risk factors of medication-related osteonecrosis of the jaw in osteoporotic and breast cancer patients: a cross-sectional study.

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) has been reported as a side effect of bisphosphonate (BP). The aim of this study was to identify the prevalence of MRONJ in women taking BP for osteoporosis and for metastatic breast cancer and correlate it with risk factors and biochemical markers of bone metabolism.

Methods: Patients taking oral or intravenous BP with osteoporosis (G1; n = 153; median 72.

Subcutaneous vs Intravenous Trastuzumab for Patients With ERBB2-Positive Early Breast Cancer: Final Analysis of the HannaH Phase 3 Randomized Clinical Trial.

Importance: Confirmation of long-term comparability between subcutaneous and intravenous trastuzumab is essential.

Objective: To evaluate efficacy and safety of subcutaneous trastuzumab compared with that of intravenous trastuzumab for patients with ERBB2 (HER2)-positive early breast cancer after 6 years' follow-up in the HannaH (Enhanced Treatment With Neoadjuvant Herceptin) trial.

Design, Setting, And Participants: Open-label, prospective, multicenter, international, neoadjuvant-adjuvant, randomized, phase 3 noninferiority clinical trial (primary end points: pathologic complete response and serum trough concentration predose cycle 8) conducted for 596 patients with ERBB2-positive early breast cancer enrolled from October 19, 2009, to December 1, 2010.

Patient satisfaction with breast reconstructionusing musculocutaneous flap from latissimus dorsiversus from rectus abdominis: a cross-sectional study.

Background: Breast cancer is the second most frequent type of cancer worldwide and the most common type among women. The treatment for this condition has evolved over recent decades with therapeutic and technological advances. Breast reconstruction techniques using musculocutaneous flaps from the latissimus dorsi and rectus abdominis have aroused interest regarding patients' quality of life.

Swainsonine, an alpha-mannosidase inhibitor, may worsen cervical cancer progression through the increase in myeloid derived suppressor cells population.

Cervical cancer, caused by high oncogenic risk Human Papillomavirus (HPV) infection, continues to be a public health problem, mainly in developing countries. Using peptide phage display as a tool to identify potential molecular targets in HPV associated tumors, we identified α-mannosidase, among other enriched sequences. This enzyme is expressed in both tumor and inflammatory compartment of the tumor microenvironment.

Specific protocols of controlled ovarian stimulation for oocyte cryopreservation in breast cancer patients.

Background: Fertility preservation is an important concern in breast cancer patients. In the present investigation, we set out to create a specific protocol of controlled ovarian stimulation (cos) for oocyte cryopreservation in breast cancer patients.

Methods: From November 2014 to December 2016, 109 patients were studied.

First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial.

Purpose: To assess pertuzumab plus trastuzumab and an aromatase inhibitor (AI) in patients with human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor-positive metastatic/locally advanced breast cancer (MBC/LABC).

Patients And Methods: The PERTAIN trial (NCT01491737) is an ongoing randomized, open-label, multicenter-80 sites and eight countries-phase II trial. Patients have HER2-positive, hormone receptor-positive MBC/LABC and no prior systemic therapy with the exception of endocrine.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

Aim: To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors.

Methods And Results: This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables.

Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Clinical Trial.

Importance: Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer.

Objective: To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer.

Design, Setting, And Participants: In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014.

A specific controlled ovarian stimulation (COS) protocol for fertility preservation in women with breast cancer undergoing neoadjuvant chemotherapy.

Aim Of The Study: The authors present a novel and specific controlled ovarian stimulation protocol for fertility preservation in women with estrogen-positive receptor breast cancer undergoing neoadjuvant chemotherapy. The protocol foresees random start ovarian stimulation and the use of letrozole associated to tamoxifen.

Material And Methods: Forty breast cancer patients were included in the study.

Prime incision: A minimally invasive approach to breast cancer surgical treatment-A 2 cohort retrospective comparison with conventional breast conserving surgery.

The prime incision technique is an oncoplastic surgery aimed to remove both the breast tumor and the sentinel lymph node through one incision, thus providing better aesthetic results than the conventional breast conservative two incision technique. We retrospectively evaluated 2 cohorts of 60 consecutive breast cancer patients operated by either conventional breast conservative surgery (N = 26) or one incision surgery (N = 34). There were no recurrence or death events observed in any group.

ANDRO-IVF: a novel protocol for poor responders to IVF controlled ovarian stimulation.

Objective: This study aimed to assess a novel protocol designed to improve poor ovarian response through intra-ovarian androgenization. The endpoints were: number of oocytes and mature oocytes retrieved, fertilization, cancellation and pregnancy rates.

Methods: This prospective crossover study enrolled poor responders from previous ovarian stimulation cycles submitted to a novel protocol called ANDRO-IVF.

Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial.

Purpose: Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer.

Methods: 668 postmenopausal women with HR+, HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.

Assessment of HER-2 status in invasive breast cancer in Brazil.

Objective: To characterize the frequency of HER-2-positive breast cancer in Brazil.

Method: In this prospective observational study, we first ascertained the HER-2 status of invasive breast cancer specimens by automated immunohistochemistry (IHC). For specimens classified as 2+ by IHC, we performed in situ hybridization (ISH).

Long-Acting Reversible Contraception.

Unwanted pregnancy is a major public health problem both in developed and developing countries. Although the reduction in the rates of these pregnancies requires multifactorial approaches, increasing access to long-acting contraceptive methods can contribute significantly to change this scenario. In Brazil, gynecologists and obstetricians play a key role in contraceptive counseling, being decisive in the choice of long-acting reversible methods, characterized by intrauterine devices (IUDs) and the contraceptive implant.

A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).

Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models.

Patients And Methods: BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease.

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.

Inhibition of EGFR, HER2, and HER3 signaling with AZD8931 in combination with anastrozole as an anticancer approach: Phase II randomized study in women with endocrine-therapy-naïve advanced breast cancer.

Purpose: AZD8931 is an orally bioavailable, reversible tyrosine kinase inhibitor of EGFR, HER2, and HER3 signaling. The Phase II MINT study (ClinicalTrials.gov NCT01151215) investigated whether adding AZD8931 to endocrine therapy would delay development of endocrine resistance in patients with hormone-sensitive advanced breast cancer.

HannaH phase III randomised study: Association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up.

Background: In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (pCR). Evidence suggests that pCR, particularly total pCR (tpCR), is likely to predict clinical benefit. We report associations between tpCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety.

Skin disorders during menopause.

Menopause is the cessation of menstrual periods due to the loss of ovarian function. Among the various phases of a woman's life, menopause has the greatest impact on health and has been one of the most neglected areas of research. Hormonal changes caused by menopause can lead to problems in the skin and its annexes, and despite the high frequency of dermatologic signs and symptoms, studies on this topic are limited.

Lymph node micrometastases in initial stage cervical cancer and tumoral recurrence.

Objective: To evaluate the prevalence of micrometastases in lymph node tissue of patients with stage Ib1-IIA cervical cancer, the correlation of micrometastases with tumor recurrence and survival, and the expression of D2-40 in the primary tumor of patients with recurrence and/or micrometastases and its correlation with histopathologic findings.

Methods: In a retrospective study, the medical records of all patients with cervical cancer treated at a hospital in São Paulo, Brazil, between 2001 and 2007 were reviewed. Patients with no lymph node metastases and treated with radical hysterectomy without adjuvant treatment were included.

Intraoperative full-dose of partial breast irradiation with electrons delivered by standard linear accelerators for early breast cancer.

Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of intraoperative radiotherapy (IORT) with electrons delivered by standard linear accelerators (Linacs) during breast conserving surgeries for early infiltrating breast cancer (BC) treatment. Materials and Methods.

Intraoperative radiation therapy in early breast cancer using a linear accelerator outside of the operative suite: an "image-guided" approach.

Purpose: To present local control, complications, and cosmetic outcomes of intraoperative radiation therapy (IORT) for early breast cancer, as well as technical aspects related to the use of a nondedicated linear accelerator.

Methods And Materials: This prospective trial began in May of 2004. Eligibility criteria were biopsy-proven breast-infiltrating ductal carcinoma, age >40 years, tumor <3 cm, and cN0.

Laparoscopy as the most effective tool for management of postmenopausal complex adnexal masses when expectancy is not advisable.

Postmenopausal women with adnexal masses suspicious for malignancy must undergo surgery for histopathologic confirmation. The low positive predictive value for malignancy of the currently available preoperative examinations results in 5 to 220 surgeries performed for each case of pelvic malignancy detected, depending on the evaluation method and patient selection. Although extensively reviewed as an effective tool for the investigation and treatment of adnexal masses, laparoscopy is still underused for this purpose in postmenopausal women.

Brazilian residents' attitude and practice toward sexual health issues in pregnant patients.

Introduction: Sexual difficulties and questions regarding sexual function are frequent in pregnancy, yet they are infrequently discussed in academic communities, medical schools, and residency programs. Embarrassment, lack of experience, inadequate communication skills and insufficient knowledge on how to deal with sexual complaints, and questions in pregnancy are common, especially among young health professionals.

Aim: The aim of this study was to assess and compare the attitude and behavior of Brazilian residents in three different medical programs (obstetrics-gynecology, internal medicine, and psychiatry) toward sexual health issues of pregnant patients.