Prognostic Factors and Survival Outcomes of Patients With Early HER2+ Breast Cancer Treated With Trastuzumab in a Brazilian Public Reference Center: A Real-World Study.

PURPOSE: Trastuzumab was introduced into the Brazilian public health care service for early breast cancer (BC) in 2012. This study describes the survival outcomes and prognostic factors related to early HER2+ BC treatment in a Brazilian reference cancer center. PATIENTS AND METHODS: This were a retrospective, single-center, observational study of early HER2+ BC patients treated with trastuzumab in the (neo)adjuvant setting between 2012 and 2018 at Hospital Pérola Byington. Demographic, clinical, disease-free survival (DFS) and overall survival (OS) data were evaluated. Multivariate analysis was performed to assess independent prognostic factors. RESULTS: One hundred seventy-six and 353 patients treated in the neoadjuvant and adjuvant setting were included, respectively. The 3- and 5-year OS rates were 79% and 56% for the neoadjuvant group and 97% and 92% for the adjuvant group, respectively. Node positivity at diagnosis predicted poor OS for both groups. In the neoadjuvant group, stage III disease at diagnosis, delayed surgery, and lack of pathological complete response (pCR) predicted poor prognosis. The 3- and 5-year DFS rates were 67% and 46% in the neoadjuvant group and 91% and 86% in the adjuvant group, respectively. Histological grade 2, stage III disease at diagnosis, and lack of pCR predicted poor DFS for the neoadjuvant group. For the adjuvant group, node positivity at diagnosis predicted poor DFS. CONCLUSION: Our results reveal multiple clinical parameters affecting survival outcomes according to the treatment setting. Patients treated with neoadjuvant therapy have a poor prognosis since they present with more advanced disease, indicating the importance of early diagnosis and optimized treatment.

Diagnosing molecular subtypes of breast cancer by means of Raman spectroscopy.

OBJECTIVES: Raman spectroscopy has been used to discriminate human breast cancer and its different tumor molecular subtypes (luminal A, luminal B, HER2, and triple-negative) from normal tissue in surgical specimens. MATERIALS AND METHODS: Breast cancer and normal tissue samples from 31 patients were obtained by surgical resection and submitted for histopathology. Before anatomopathological processing, the samples had been submitted to Raman spectroscopy (830 nm, 25 mW excitation laser parameters). In total, 424 Raman spectra were obtained. Principal component analysis (PCA) was used in an exploratory analysis to unveil the compositional differences between the tumors and normal tissues. Discriminant models were developed to distinguish the different cancer subtypes by means of partial least squares (PLS) regression. RESULTS: PCA vectors showed spectral features referred to the biochemical constitution of breast tissues, such as lipids, proteins, amino acids, and carotenoids, where lipids were decreased and proteins were increased in breast tumors. Despite the small spectral differences between the different subtypes of tumor and normal tissues, the discriminant model based on PLS was able to discriminate the spectra of the breast tumors from normal tissues with an accuracy of 97.3%, between luminal and nonluminal subtypes with an accuracy of 89.9%, between nontriple-negative and triple-negative with an accuracy of 94.7%, and each molecular subtype with an accuracy of 73.0%. CONCLUSION: PCA could reveal the compositional difference between tumors and normal tissues, and PLS could discriminate the Raman spectra of breast tissues regarding the molecular subtypes of cancer, being a useful tool for cancer diagnosis.

Substantial Reduction in Adjuvant Chemotherapy With the Use of the 21-Gene Test to Manage Early Breast Cancer in a Public Hospital in Brazil.

PURPOSE: We evaluated the impact of 21-gene test results on treatment decisions for patients with early-stage breast cancer treated under the public health care system in Brazil, Sistema Único de Saúde. METHODS: Eligible patients treated at Hospital Pérola Byington and Santa Casa de Misericórdia de São Paulo in Brazil were required to have the following characteristics: postsurgery with hormone receptor-positive, human epidermal growth factor 2-negative, node-negative and node-positive, and T1/T2 breast cancer and patients with these characteristics were candidates for adjuvant systemic therapy. Treatment recommendations, chemotherapy plus hormonal therapy (CT + HT) or HT alone, were captured before and after 21-gene test results. RESULTS: From August 2018 to April 2019, 179 women were enrolled. The mean age was 58 years (29-86 years), 135 (76%) were postmenopausal, and 58 (32%) had node-positive breast cancer. Most patients (61%) had a tumor > 2 cm, including 7% with tumors > 4 cm. Using Recurrence Score (RS) result cut points on the basis of the TAILORx trial, 40 (22%) had RS 0-10, 91 (51%) had RS 11-25, and 48 (27%) had RS 26-100. Before 21-gene testing, 162 of 179 (91%) patients were recommended for CT. After testing, 117 of 179 patients (65%) had changes in CT recommendation: 112 (63%) who were initially recommended CT received HT alone and five (3%) who were initially recommended HT alone received CT + HT. After 21-gene testing, 99% of physicians reported strong confidence in their treatment recommendations. CONCLUSION: The change in clinical practice at these public hospitals was greater than expected: 66% of initial treatment recommendations were changed to omit CT with 21-gene test results. Clinicopathologic features did not correlate well with 21-gene test results and did not adequately identify those most likely to benefit from CT.

The impact of letrozole administration on oocyte morphology in breast cancer patients undergoing fertility preservation.

ABSTRACT: Patients submitted to oncological fertility preservation with letrozole and gonadotropins seem to present a higher rate of immature oocytes and lower fertilization rates in comparison to infertile patients submitted to IVF cycles with gonadotropins. The aim of this study was to evaluate the influence of letrozole on oocyte morphology in patients with breast cancer submitted to fertility preservation. METHODS: Retrospective analysis performed at a public tertiary hospital in São Paulo, Brazil. The oocytes were retrieved from patients with breast cancer undergoing fertility preservation (n=69), and from infertile women undergoing in vitro fertilization (n=92). We evaluated 750 oocytes obtained from breast cancer patients submitted to ovarian stimulation with letrozole and gonadotropins, and 699 oocytes from patients without breast cancer submitted to ovarian stimulation for in vitro fertilization with gonadotropins only due to male factor infertility. The mature oocytes retrieved were analyzed for the presence of refractile bodies, ooplasm color and regularity, central granulation degree, cortical granules, zona pellucida staining and regularity, perivitelline space, presence of vacuoles or abnormal smooth-surfaced endoplasmic reticle and oocyte retraction. RESULTS: There was a higher incidence of alterations in oocyte morphology in the letrozole group when compared to the control group: increased perivitelline space (p=0.007), irregular zona pellucida (p<0.001), refractile bodies (p<0.001), dark ooplasm (p<0.001), granular ooplasm (p<0.001), irregular ooplasm (p<0.001) and dense central granulation (p<0.001). CONCLUSION: Letrozole is a risk factor for worse oocyte morphology. However, the clinical impact of ovarian stimulation protocol with combined use of gonadotropins and letrozole for fertility preservation remains unclear in this setting. These data underline the importance of establishing the predictive potential of morphological dimorphisms of human oocytes in IVF outcomes.

Preimplantation genetic diagnosis for a patient with multiple endocrine neoplasia type 1: case report.

Preimplantation genetic diagnosis was carried out for embryonic analysis in a patient with multiple endocrine neoplasia type 1 (MEN1). This is a rare autosomal-dominant cancer syndrome and the patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues, associated with germline and somatic inactivating mutations in the MEN1 gene. This case report documents a successful preimplantation genetic diagnosis (PGD) involving a couple at-risk for MEN1 syndrome, with a birth of a healthy infant. The couple underwent a cycle of controlled ovarian stimulation and intracytoplasmic sperm injection (ICSI). Embryos were biopsied at the blastocyst stage and cryopreserved; we used PCR-based DNA analysis for PGD testing. Only one of the five embryos analyzed for MEN1 syndrome was unaffected. This embryo was thawed and transferred following endometrial preparation. After positive ßHCG test; clinical pregnancy was confirmed by ultrasound, and a healthy infant was born. PGD for single gene disorders has been an emerging therapeutic tool for couples who are at risk of passing a genetic disease on to their offspring.

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. COS was performed either with recombinant FSH or hMG. Concomitantly with COS, letrozole in a dose of 5 mg and tamoxifen in a dose of 20 mg were given orally on a daily basis. The trigger was performed with 0.2 mg of triptorelin, in the presence of follicles ≥ 19 mm. Oocyte retrieval was scheduled 35-36 hours after triptorelin injection. Our main outcome measures were the number of oocytes collected and number of oocytes vitrified, the length of ovarian stimulation, total dose of gonadotropins administered, and levels of estradiol on the day of the trigger. RESULTS: The mean age of patients was 30.43 ±4.25 years. Nineteen women commenced COS in the luteal phase, eleven in the early follicular phase and ten in the late follicular phase. The mean number of collected oocytes was 11.78 ±9.12 and the mean number of vitrified oocytes was 9.72 ±7.36. The mean duration of COS was 10.03 ±1.33 days. The mean estradiol concentrations on the triggering day was 623.10 ±441.27, and the mean dose of gonadotropins administered was 2540 ±713.10. CONCLUSIONS: The authors suggest that the protocol is efficient and may be a safe option for oocyte vitrification in these patients.

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. Tumor sections were reviewed and lymph nodes were analyzed with AE1/AE3. Patients with and without recurrence were compared. The presence of lymph node micrometastasis or isolated tumor cells was also evaluated. RESULTS: Of the 83 patients evaluated, 15 (18%) had recurrence. Significant differences between patients with and without recurrence were observed with regard to tumor greatest axis, clinical stage, number of micrometastases, and negative lymph nodes (P≤0.04). Lymph node micrometastases and isolated tumor cells were significantly different for a stromal invasion depth greater than 2/3 (P=0.046). CONCLUSION: The presence of lymph node micrometastases is an important risk factor for tumor recurrence. These patients should be considered eligible for adjuvant radiochemotherapy treatment.

Evaluation of bone metastases from breast cancer by bone scintigraphy and positron emission tomography/computed tomography imaging.

OBJECTIVE: The aim of this study was to compare bone scintigraphy (BS) and positron emission tomography/computed tomography (PET/CT) for the detection of bone metastases from breast cancer. STUDY DESIGN: Twenty patients with breast cancer and bone pain were submitted to both bone scintigraphy and 18-F-fluorodeoxyglucose PET/CT imaging between July 2012 and June 2013. Scintigraphy was performed following an intravenous injection of technetium-99m-methylene diphosphonate (99mTc-MDP) around 10 days before the PET/CT scan, performed using an intravenous injection of 18-F-fluorodeoxyglucose followed by whole-body computed tomography (CT) to characterize metastases by both methods. Student's t-test for paired samples was used in the comparative data analysis, with significance at p<0.05. RESULTS: CT identified 429 metastatic implants in the 20 patients, with scintigraphy showing 244 of these lesions (57%) and PET/CT showing 307 (72%); however, there was no statistically significant difference between the mean number of lesions detected per patient with the two imaging modalities (p=0.367). CONCLUSION: In the present study, no difference was found between PET/CT and bone scintigraphy in the detection of bone metastases from breast cancer.

Correlation Between Anthropometric Measures and Biomarker Changes After Neoadjuvant Therapy With Tamoxifen or Anastrozole in Postmenopausal Women With Breast Cancer.

BACKGROUND: Epidemiological studies have reported positive associations between anthropometric measures and risk for developing breast cancers that express hormone receptors and associated mortality. However, the impact of nutritional status on the molecular response to endocrine therapy has yet to be described. METHODS: Body mass index (BMI), waist circumference (WC), hip circumference (HP), and waist-to-hip ratio (WHR) were measured in patients with invasive ductal carcinoma (IDC) before and after neoadjuvant treatment with either tamoxifen or anastrozole, and a possible correlation with prognostic factors, as estrogen receptor (ER), progesterone receptor (PgR), and proliferative index (Ki-67), was analyzed. Fifty-seven patients with palpable ER-positive IDC were randomized into three neoadjuvant treatment groups and received anastrozole or placebo or tamoxifen for twenty-one days. Biomarker status was obtained by comparing the immunohistochemical evaluation of samples collected before and after treatment, using the Allred scoring system. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS). RESULTS AND CONCLUSIONS: After treatment, the anastrozole group showed reduced ER and PgR expression (p < 0.05), and both the anastrozole and tamoxifen groups showed lower Ki-67 status. A significant reduction in PgR positivity (p < 0.05) was found in women with large WC and HC who were treated with anastrozole. Reduction in PgR positivity also tended to be associated with BMI (p = 0.09) in the anastrozole group. BMI, WC, HC and WHR correlated neither with biomarker levels in the tamoxifen and placebo groups nor with ER and Ki-67 status in the anastrozole group after primary endocrine treatment.

High pregnancy rates with consecutive (two-step) embryo transfer in assistide reproductive technologies: preliminary results

Objetivo: O objetivo deste trabalho é verificar se a transferência embrionária dupla (consecutiva) pode proporcionar taxas de gravidez mais altas em técnicas de reprodução assistida. Material e métodos: Um total de 30 pacientes que tiveram 4 ou mais embriões para transferência no dia 3 após a coleta oocitária, foram submetidas a transferência embrionária dupla (consecutiva). Foram trasnferidos 3 embriões no dia 3 e um blastocisto no dia 5. Foram avaliadas as taxas de gravidez e implantação, determinadas pela visibilizaçào ecográfica de batimentos cardíacos fetais. Resultados: Dentre as 30 transferências embrionárias, houve 14 gestações (46,7%), sendo 4 (28,5%) únicas, 8 gemelares (57,1%) e 2 trigemelares (14,2%). Conclusões: Nossos resultados preliminares sugerem que a transferência consecutiva não apenas não afeta negativamente o processo de implantação embrionária, mas também relaciona-se com altas taxas de gravidez

Molecular biology and gynecology: CD 36 and its interactions with tamoxifen

Tamoxifen (TAM) is an antiestrogenic drug widely used in breast cancer treatment. By using the Differential Display technique in normal and malignant breast tissues, before and during TAM therapy, we were able to demonstrate that expression of the CD36 gene is down-regulated by this drug. CD36 is a cell-surface glycoprotein that acts as a receptor for thrombospondin-1, oxidized-LDL and collagens type I and IV. Thrombospondin-1 is involved in invasion, metastasis and angiogenesis and therefore the down-regulation of CD36 induced by TAM, might correspond to an alternative mechanism of action of this drug. CD36 is also one of the receptors for the oxidized-LDL which in turn is involved in pathogenesis of arteriosclerosis; thus the down-regulation of CD36 during TAM might explain the at least in part the lower levels of myocardial infarction during its use.

Aspectos clínicos e terapêuticos do carcinoma de mama em pacientes idosas: estudo de 72 casos / Clinical and therapeutic aspects of breast carcinoma in elderly patients: study of 72 cases

O carcinoma de mama na paciente idosa apresenta crescente incidência e, ao contrário das jovens, aumento nos índices de mortalidade. Estudou-se 72 pacientes com idade superior a 65 anos, tratadas no Setor de Mastologia da Disciplina de Ginecologia da Escola Paulista de Medicina, de janeiro de 1990 a janeiro de 1994. O diagnóstico foi tardio em 62 por cento das pacientes e o comprometimento linfonodal axilar foi de 51,7 por cento. A mastectomia com linfadenectomia foi a cirurgia de escolha com mortalidade inferior a 1 por cento e controle loco-regional em 40 meses de 93,7 por cento. Indicou-se a radioterapia apenas como complemento da quadrantectomia ou de casos avançados. No tratamento sistêmico empregou-se, preferencialmente, tamoxifeno (20 mg/dia) por tempo mínimo de 24 meses. Os autores ressaltam ainda a importância do rastreamento da neoplasia endometrial nessas pacientes. A quimioterapia ficou restrita a pacientes em bom estado geral com tumores inoperáveis e hormônio resistentes.