RESUMO
OBJECTIVE: To evaluate the change in adjuvant therapeutic decision in a cohort of young women with breast cancer discussed by a multidisciplinary team, before and after EndoPredict testing. PATIENTS AND METHODS: 99 premenopausal women with hormone receptor-positive, HER2-negative, T1-T2, and N0-N1 breast cancer were included. Clinicopathological characteristics were recorded and cases were presented in a multidisciplinary tumor board. Consensual therapeutic decisions before and after EndoPredict results were registered. Medical records were reviewed at six-month follow-up to determine physicians' adherence to therapeutic recommendations. Pearson chi-square and McNemar's tests were used to analyze differences between groups and changes in treatment recommendations, respectively. RESULTS: Median age at diagnosis was 43 years. The most frequent tumor size was pT2 (53.5%) and 27% of patients had 1-3 positive lymph nodes. 46% of patients had a low-risk EPclin result. Nodal status and tumor grade were significantly associated with EPclin result (p < .00001 and p = .0110, respectively), while Ki67 levels and age ≤40 years were not. A change in chemotherapy decision was registered in 19.2% of patients (p = .066), with the greatest impact in de-escalation (9% net reduction). A change in chemotherapy or endocrine therapy regimen was suggested in 19% and 20% of cases, respectively, after EPclin results were available. A significant difference was found in the median EPclin score between patients with a low- vs. high-intensity chemotherapy and endocrine therapy regimen recommendation (p = 0.049 and p = 0.0001, respectively). Tumor board treatment recommendation adherence with the EndoPredict result was 95% and final treatment adherence to EPclin result was 93%. CONCLUSIONS: The EndoPredict test successfully assisted the clinical decision-making process in premenopausal patients, with a clinically significant change in overall decision-making, with the greatest impact seen in chemotherapy reduction, and a high rate of therapeutic adherence.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Tomada de Decisão Clínica , Pré-Menopausa , Transcriptoma , Adulto , Neoplasias da Mama/metabolismo , Estudos de Coortes , Tomada de Decisões , Feminino , Humanos , México , Pessoa de Meia-Idade , Gradação de TumoresAssuntos
Neoplasias da Mama , Sobreviventes de Câncer , Internet , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Humanos , Informática Médica/estatística & dados numéricos , México , Pessoa de Meia-Idade , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: It has become evident that intra-tumor heterogeneity of breast cancer impact on several biological processes such as proliferation, migration, cell death and also might contribute to chemotherapy resistance. The expression of Receptor Tyrosine Kinases (RTKs) has not been analyzed in the context of intra-tumor heterogeneity in a primary breast cancer cell culture. Several subpopulations were isolated from the MBCDF (M serial-breast cancer ductal F line) primary breast cancer cells and were successfully maintained in culture and divided in two groups according to their morphology and RTKs expression pattern, and correlated with biological processes like proliferation, migration, anchorage-independent cell growth, and resistance to cytotoxic chemotherapy drugs and tyrosine kinase inhibitors (TKIs). METHODS: Subpopulations were isolated from MBCDF primary breast cancer cell culture by limiting dilution. RTKs and hormone receptors were examined by Western blot. Proliferation was measure by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT assay). Cell viability was evaluated by Crystal Violet. Migration was assessed using Boyden chambers. Anchorage-independent cell growth was evaluated by colony formation in soft agar. RESULTS: Several subpopulations were isolated from the MBCDF breast cancer cells that were divided into two groups according to their morphology. Analysis of RTKs expression pattern showed that HER1, HER3, c-Met and VEGFR2 were expressed exclusively in cells from group 1, but not in cells from group 2. PDGFR was expressed only in cells from group 2, but not in cells from group 1. HER2, HER4, c-Kit, IGF1-R were expressed in all subpopulations. Biological processes correlated with the RTKs expression pattern. Group 2 subpopulations present the highest rate of cell proliferation, migration and anchorage-independent cell growth. Analysis of susceptibility to chemotherapy drugs and TKIs showed that only Paclitaxel and Imatinib behaved differently between groups. Group 1-cells were resistant to both Paclitaxel and Imatinib. CONCLUSIONS: We demonstrated that subpopulations from MBCDF primary cell culture could be divided into two groups according to their morphology and a RTKs excluding-expression pattern. The differences observed in RTKs expression correlate with the biological characteristics and chemoresistance of each group. These results suggest that intra-tumor heterogeneity contributes to generate groups of subpopulations with a more aggressive phenotype within the tumor.
Assuntos
Neoplasias da Mama/patologia , Mesilato de Imatinib/farmacologia , Paclitaxel/farmacologia , Cultura Primária de Células/métodos , Receptores Proteína Tirosina Quinases/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Heterogeneidade Genética , Humanos , Receptores Proteína Tirosina Quinases/genética , Células Tumorais CultivadasRESUMO
PURPOSE OF REVIEW: Because of the recognized impact of breast cancer and its treatment on a young woman's life, initiatives are being established worldwide. The main aim of this review was to describe existing specialized programs that support young women with breast cancer (YWBC), advances to date, current challenges and future actions. RECENT FINDINGS: Current programs for YWBC are now educating professionals, patients, and communities on their specific needs. Also, support groups have helped break isolation and connect YWBC together. Research on biology, treatment, adverse effects, risk factors, genetics, and social aspects on YWBC is now being actively conducted. In low- and middle-income countries, the particular issues of young women are, however, still not systematically addressed, because of scarce funding, lack of awareness of YWBC needs, and deficient provider training. SUMMARY: Practice guidelines and algorithms should be disseminated and available for their widespread use to allow standard clinical and supportive care for YWBC even in oncologic centers where no specific programs exist. Also, cancer centers should formally commit to financing, at least partially, dedicated services, and existing programs for YWBC, guaranteeing their continuity. Finally, interinstitutional and international collaborations should be encouraged to facilitate adequately powered research, to avoid repetitive efforts, and to promote knowledge sharing and translation.