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1.
Oncologist ; 28(2): 172-179, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36493359

RESUMO

In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive activation, far less is known about the molecular functions and clinical consequences of ESR1 fusions (ESR1-FUS). This case series discusses 4 patients with HR+ MBC with ESR1-FUS in the context of the existing ESR1-FUS literature. We consider therapeutic strategies and raise the hypothesis that CDK4/6 inhibition (CDK4/6i) may be effective against ESR1-FUS with functional ligand-binding domain swaps. These cases highlight the importance of screening for ESR1-FUS in patients with HR+ MBC while continuing investigation of precision treatments for these genomic rearrangements.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Receptor alfa de Estrogênio/genética , Mutação
2.
Breast Cancer Res Treat ; 199(3): 501-509, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37103597

RESUMO

PURPOSE: Patients with breast cancer (BC) face complex medical information and decisions. The Outcomes4Me mobile app provides evidence-based BC education, symptom management tracking and clinical trial matching. This study sought to evaluate the feasibility of introducing this app into routine BC care. METHODS: In this pilot study among BC patients undergoing therapy at an academic cancer center, patients were followed for 12 weeks with survey administration and electronic health record (EHR) abstraction at baseline and completion. Feasibility was defined as 40% of patients engaging with the app 3 or more times during the study. Additional endpoints included app usability (system usability scale), patient care experience, symptom evaluation, and clinical trial matching. RESULTS: The study enrolled 107 patients from 6/01/2020 to 3/31/2021. Utilization of the app was deemed feasible with 60% of patients engaging with the app at least 3 times. SUS score of 70 indicated above average usability. New diagnosis and higher education level was associated with greater app engagement, with usability similar across all age groups. 41% of patients found the app helped track symptoms. Cognitive and sexual symptoms were infrequently reported, but were more frequently captured in the app than in the EHR. After using the app, 33% of patients reported increased interest in clinical trial enrollment. CONCLUSION: Introducing the Outcomes4Me patient navigation app into routine BC care is feasible and may improve the patient experience. These results support further evaluation of this mobile technology platform to improve BC education, symptom management, and decision making. CLINICAL TRIAL REGISTRY: Clinicaltrials.gov registration #: NCT04262518.


Assuntos
Neoplasias da Mama , Aplicativos Móveis , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Estudos de Viabilidade , Projetos Piloto , Smartphone
3.
Ann Surg Oncol ; 30(10): 5951-5961, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37495843

RESUMO

Breast cancer patients are living longer than ever before and as such the population of breast cancer survivors continues to grow. Approximately 80% of breast cancers are hormone receptor-positive (HR+) and most patients will receive neoadjuvant or adjuvant estrogen blockade, referred to as endocrine therapy. Although endocrine therapy reduces HR+ breast cancer recurrence by 30-50%, significant adverse effects pose a threat to treatment adherence. These adverse effects include vasomotor symptoms, colloquially referred to as hot flashes, bone loss, joint arthralgias, genitourinary syndrome of menopause (GSM), previously referred to as vaginal atrophy, and low libido. This review will present the evidence-based treatments available for each of these adverse effects, including clear treatment algorithms for GSM, which is often experienced by patients but overlooked by providers. The most important takeaway is to ask open-ended questions, encourage reporting of these symptoms, and refer patients to specialty providers as needed. Surgeons may be the first to encounter these symptoms, therefore it is critical to remain informed of the treatment options.


Assuntos
Neoplasias da Mama , Cirurgiões , Feminino , Humanos , Recidiva Local de Neoplasia , Menopausa , Fogachos/induzido quimicamente , Fogachos/terapia , Neoplasias da Mama/tratamento farmacológico
4.
Oncologist ; 27(11): 930-939, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-35852437

RESUMO

BACKGROUND: Precision oncology relies on molecular diagnostics, and the value-proposition of modern healthcare networks promises a higher standard of care across partner sites. We present the results of a clinical pilot to standardize precision oncology workflows. METHODS: Workflows are defined as the development, roll-out, and updating of disease-specific molecular order sets. We tracked the timeline, composition, and effort of consensus meetings to define the combination of molecular tests. To assess clinical impact, we examined order set adoption over a two-year period (before and after roll-out) across all gastrointestinal and hepatopancreatobiliary (GI) malignancies, and by provider location within the network. RESULTS: Development of 12 disease center-specific order sets took ~9 months, and the average number of tests per indication changed from 2.9 to 2.8 (P = .74). After roll-out, we identified significant increases in requests for GI patients (17%; P < .001), compliance with testing recommendations (9%; P < .001), and the fraction of "abnormal" results (6%; P < .001). Of 1088 GI patients, only 3 received targeted agents based on findings derived from non-recommended orders (1 before and 2 after roll-out); indicating that our practice did not negatively affect patient treatments. Preliminary analysis showed 99% compliance by providers in network sites, confirming the adoption of the order sets across the network. CONCLUSION: Our study details the effort of establishing precision oncology workflows, the adoption pattern, and the absence of harm from the reduction of non-recommended orders. Establishing a modifiable communication tool for molecular testing is an essential component to optimize patient care via precision oncology.


Assuntos
Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão/métodos , Fluxo de Trabalho , Oncologia/métodos , Atenção à Saúde
5.
J Natl Compr Canc Netw ; 20(6): 723-734, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35714678

RESUMO

The role of neoadjuvant therapy (NAT) for localized breast cancer has evolved tremendously over the past several years. Currently, NAT is the preferred option for high-risk early triple-negative (TN) and HER2-positive (HER2+) breast cancers and is indicated for some estrogen receptor-positive (ER+) breast cancers. In addition to traditional absolute indications for NAT, relative indications such as the assessment of outcomes at the time of surgery and guidance of treatment escalation and de-escalation have greatly evolved in recent years. Pathologic complete response (pCR) and the Residual Cancer Burden (RCB) index are highly prognostic for disease recurrence and survival, mainly in patients with TN or HER2+ disease. Furthermore, post-NAT escalation strategies have been shown to improve long-term outcomes of patients who do not achieve pCR. Additionally, by allowing the direct assessment of drug effect on the tumor, the neoadjuvant setting has become an attractive setting for the exploration of novel agents and the identification of predictive biomarkers. Neoadjuvant trial design has also evolved, using adaptive treatment approaches that enable treatment de-escalation or escalation based on response. However, despite multiple practice-changing neoadjuvant trials and the addition of various new agents to the neoadjuvant setting for early breast cancer, many key questions remain. For example, patient selection for neoadjuvant immunotherapy in TN breast cancer, de-escalation methods in HER2+ breast cancer, and the use of gene expression profiles to guide NAT recommendations in ER+ breast cancer. This article reviews the current approach for NAT in localized breast cancer as well as evolving NAT strategies, the key remaining challenges, and the ongoing work in the field.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Receptor ErbB-2/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
6.
Breast Cancer Res ; 23(1): 85, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34392831

RESUMO

In metastatic hormone receptor-positive breast cancer, ESR1 mutations are a common cause of acquired resistance to the backbone of therapy, estrogen deprivation by aromatase inhibition. How these mutations affect tumor sensitivity to established and novel therapies are active areas of research. These therapies include estrogen receptor-targeting agents, such as selective estrogen receptor modulators, covalent antagonists, and degraders (including tamoxifen, fulvestrant, and novel agents), and combination therapies, such as endocrine therapy plus CDK4/6, PI3K, or mTORC1 inhibition. In this review, we summarize existing knowledge surrounding the mechanisms of action of ESR1 mutations and roles in resistance to aromatase inhibition. We then analyze the recent literature on how ESR1 mutations affect outcomes in estrogen receptor-targeting and combination therapies. For estrogen receptor-targeting therapies such as tamoxifen and fulvestrant, ESR1 mutations cause relative resistance in vitro but do not clearly lead to resistance in patients, making novel agents in this category promising. Regarding combination therapies, ESR1 mutations nullify any aromatase inhibitor component of the combination. Thus, combinations using endocrine alternatives to aromatase inhibition, or combinations where the non-endocrine component is efficacious as monotherapy, are still effective against ESR1 mutations. These results emphasize the importance of investigating combinatorial resistance, challenging as these efforts are. We also discuss future directions and open questions, such as studying the differences among distinct ESR1 mutations, asking how to adjust clinical decisions based on molecular surveillance testing, and developing novel therapies that are effective against ESR1 mutations.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Mutação , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico
7.
Lancet ; 395(10226): 817-827, 2020 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-32145796

RESUMO

The development and approval of cyclin-dependent kinase (CDK) 4 and 6 inhibitors for hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer represents a major milestone in cancer therapeutics. Three different oral CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, have significantly improved progression-free survival by a number of months when combined with endocrine therapy. More recently, improvement in overall survival has been reported with ribociclib and abemaciclib. The toxicity profile of all three drugs is well described and generally easily manageable with dose reductions when indicated. More myelotoxicity is observed with palbociclib and ribociclib, but more gastrointestinal toxicity is observed with abemaciclib. Emerging data is shedding light on the resistance mechanisms associated with CDK4/6 inhibitors, including cell cycle alterations and activation of upstream tyrosine kinase receptors. A number of clinical trials are exploring several important questions regarding treatment sequencing, combinatorial strategies, and the use of CDK4/6 inhibitors in the adjuvant and neoadjuvant settings, thereby further expanding and refining the clinical application of CDK4/6 inhibitors for patients with breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Feminino , Previsões , Humanos , Receptores de Estrogênio , Receptores de Progesterona
8.
Oncologist ; 26(10): 827-834, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34176192

RESUMO

Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate that contains the irinotecan active metabolite, SN-38, linked to a humanized monoclonal antibody targeting trophoblast cell surface antigen 2, which is overexpressed in many solid tumors. In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single-agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan-hziy (TRODELVY) for the treatment of patients with metastatic triple-negative breast cancer who had received at least two prior therapies in the metastatic setting. Recently, results of the phase III trial, ASCENT, were confirmatory. There is limited available information on the adverse event management with sacituzumab govitecan needed to maximize the dose and duration of effective therapy while maintaining patient quality of life. This review summarizes the clinical development and the practical management of patients receiving sacituzumab govitecan. Sacituzumab govitecan has a well-defined and manageable toxicity profile, and rapid recognition and appropriate early and proactive management will allow clinicians to optimize sacituzumab govitecan treatment for patients. IMPLICATIONS FOR PRACTICE: Sacituzumab govitecan (TRODELVY) is a novel antibody-drug conjugate composed of the active metabolite of irinotecan (SN-38) conjugated to a monoclonal antibody targeting trophoblast cell surface antigen 2, an epithelial cell surface antigen overexpressed in many cancers. Because of the rapid approval of sacituzumab govitecan, there is limited available information on adverse event (AE) management with this agent. As such, this article reviews the clinical development of the drug, the AE profile, and provides recommendations regarding AE management to help optimize therapy with sacituzumab govitecan.


Assuntos
Imunoconjugados , Neoplasias de Mama Triplo Negativas , Anticorpos Monoclonais Humanizados , Camptotecina/análogos & derivados , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Imunoconjugados/efeitos adversos , Qualidade de Vida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
9.
Oncologist ; 26(10): 818-824, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34176200

RESUMO

Enhanced understanding of the molecular events underlying oncogenesis has led to the development of "tumor-agnostic" treatment strategies, which aim to target a tumor's genomic profile regardless of its anatomic site of origin. A classic example is the translocation resulting in an ETV6-NTRK3 gene fusion, a characteristic driver of a histologically diverse array of cancers. The chimeric ETV6-NTRK3 fusion protein elicits constitutive activation of the tropomyosin receptor kinase (TRK) C protein, leading to increased cell survival, growth, and proliferation. Two TRK inhibitors, larotrectinib and entrectinib, are currently approved for use in the metastatic setting for the treatment of advanced solid tumors harboring NTRK fusions. Here we report a rare case of recurrent secretory carcinoma of the breast (SCB) with NTRK3 gene fusion. Whereas most cases of SCB represent slow-growing tumors with favorable outcomes, the case detailed here is the first to the authors' knowledge of recurrence within 1 year of surgery. We review the molecular findings and potential clinical significance. KEY POINTS: The translocation resulting in the ETV6-NTRK3 gene fusion is a known oncogenic driver characteristic of secretory carcinoma of the breast (SCB). Whereas most cases of SCB represent slow-growing tumors with favorable outcomes, the case here with ETV6-NTRK3 gene fusion had local recurrence within 1 year of surgery. Two tropomyosin receptor kinase (TRK) inhibitors, larotrectinib and entrectinib, are approved to treat NTRK fusion-positive tumors, demonstrating sustained high overall response rates in the metastatic setting. Approval of TRK inhibitors necessitates optimization of NTRK fusion detection assays, including detection with liquid biopsies.


Assuntos
Neoplasias da Mama , Carcinoma , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Fusão Gênica , Humanos , Proteínas de Fusão Oncogênica/genética , Receptores Proteína Tirosina Quinases
10.
Breast Cancer Res Treat ; 188(2): 561-569, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33830393

RESUMO

BACKGROUND: Fewer than 1% of all breast cancers occur in men. As a result, a distinct lack of data exists regarding the management and outcomes in this cohort. METHODS: Any male patient with pathologically confirmed breast cancer diagnosed between August 2000 and October 2017 at either Massachusetts General Hospital or Brigham and Women's Hospital/Dana-Farber Cancer Institute and their affiliate satellite locations were included. Primary chart review was used to assess clinical and pathologic characteristics. Patient and treatment variables were reported via descriptive statistics. Local-regional failure (LRF), overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method. RESULTS: 100 patients were included in this study. Median follow-up was 112 months (range 1-220 months). Approximately 1/3 of patients experienced at least a 3-month delay to presentation. 83 patients ultimately underwent mastectomy as definitive surgical treatment. 46 patients received adjuvant radiation therapy, and 37 patients received chemotherapy. Of 82 hormone receptor-positive patients with invasive cancer, 94% (n = 77) received endocrine therapy. Of the fifty-eight patients who underwent genetic testing, 15 (26%) tested positive. The 5-year OS, BCSS, DFS, and LRF rates were 91.5%, 96.2%, 86%, and 4.8%, respectively. Delay to presentation was not associated with worse survival. CONCLUSIONS: Male breast cancer remains a rare diagnosis. Despite this, the majority of patients in this study received standard of care therapy and experienced excellent oncologic outcomes. Penetration for genetic testing improved over time.


Assuntos
Neoplasias da Mama Masculina , Neoplasias da Mama , Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Massachusetts , Mastectomia , Estudos Retrospectivos
11.
J Natl Compr Canc Netw ; : 1-8, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761455

RESUMO

BACKGROUND: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor-positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i. PATIENTS AND METHODS: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers. RESULTS: In the multicenter cohort, abemaciclib was well tolerated after a prior course of CDK4/6i (palbociclib)-based therapy; a minority of patients discontinued abemaciclib because of toxicity without progression (9.2%). After progression on palbociclib, most patients (71.3%) received nonsequential therapy with abemaciclib (with ≥1 intervening non-CDK4/6i regimens), with most receiving abemaciclib with an antiestrogen agent (fulvestrant, 47.1%; aromatase inhibitor, 27.6%), and the remainder receiving abemaciclib monotherapy (19.5%). Median progression-free survival for abemaciclib in this population was 5.3 months and median overall survival was 17.2 months, notably similar to results obtained in the MONARCH-1 study of abemaciclib monotherapy in heavily pretreated HR+/HER2-negative CDK4/6i-naïve patients. A total of 36.8% of patients received abemaciclib for ≥6 months. There was no relationship between the duration of clinical benefit while on palbociclib and the subsequent duration of treatment with abemaciclib. RB1, ERBB2, and CCNE1 alterations were noted among patients with rapid progression on abemaciclib. CONCLUSIONS: A subset of patients with HR+ MBC continue to derive clinical benefit from abemaciclib after progression on prior palbociclib. These results highlight the need for future studies to confirm molecular predictors of cross-resistance to CDK4/6i therapy and to better characterize the utility of abemaciclib after disease progression on prior CDK4/6i.

12.
J Oncol Pharm Pract ; 27(8): 1883-1890, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33153384

RESUMO

INTRODUCTION: The CREATE-X study, conducted in Japan and South Korea, established capecitabine as an adjuvant treatment option for patients with triple negative breast cancer (TNBC) who have residual disease (RD) following neoadjuvant anthracycline or taxane-based chemotherapy. However, there are no reports on the tolerability and outcomes of adjuvant capecitabine in the US setting following publication of the CREATE-X data. METHODS: We retrospectively collected treatment and tolerability data from the medical records of the first 23 TNBC patients who received adjuvant capecitabine for RD post neoadjuvant chemotherapy at our institution. Disease-free survival was assessed using the Kaplan-Meier method. RESULTS: The median starting dosage of capecitabine was 1871 mg/m2/day, most commonly divided into two daily doses on days 1-14 of each 21 day cycle. 34.8% of patients completed the treatment as prescribed. Side effects associated with treatment were common with 69.6% of patients experiencing hand-foot syndrome, 39.1% of patients experiencing diarrhea, and 13.0% of patients requiring hospitalization for side effects. Of 23 patients treated with adjuvant capecitabine, 34.8% completed the planned dose, 30.4% completed with dose reduction, and 34.8% discontinued early. At a median follow-up time of 14 months, the median disease-free survival was 22 months, with 30.4% of patients experiencing recurrence. CONCLUSION: Tolerability was poor overall compared to the CREATE-X cohort. Administering adjuvant capecitabine for TNBC patients with residual disease in the United States is challenging given differences in tolerability. More research is needed to understand how poor tolerability will affect the efficacy of this approach in the US population.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Humanos , Terapia Neoadjuvante , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
13.
Breast Cancer Res Treat ; 183(3): 515-524, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32712878

RESUMO

PURPOSE: During the COVID-19 pandemic, most breast surgery for benign and malignant conditions has been postponed, creating a backlog of patients who will need surgery. A fair and transparent system for assessing the risk of further delaying surgery for individual patients to prioritize surgical scheduling is needed. METHODS: Factors related to risk of delaying surgery for breast patients were identified. Scores were assigned to each factor, with higher scores indicating a greater risk from delaying surgery. REDCap and Microsoft Excel tools were designed to track and score delayed patients. RESULTS: Published data and multidisciplinary clinical judgement were used to assign risk scores based on patient and tumor factors, length of delay, and tumor response to preoperative therapy. Patients completing neoadjuvant chemotherapy were assigned the highest scores as their options for delaying surgery are most limited. Among patients receiving neoadjuvant endocrine therapy or no medical therapy, higher scores were assigned for low-estrogen receptor or high-genomic risk scores, higher grade, larger tumors, younger age and longer delay. High priority scores were assigned for progression during preoperative therapy. Low scores were assigned for re-excisions, atypical lesions and other benign indications. There was good agreement of the tool's ranking of sample patients with rankings by experienced clinicians. The tool generates risk-stratified patient lists by surgeon or institution to facilitate assignment of surgery dates. CONCLUSIONS: This tool generates a clinically consistent, risk-stratified priority list of breast surgical procedures delayed by the COVID-19 pandemic. This systematic approach may facilitate surgical scheduling as conditions normalize.


Assuntos
Neoplasias da Mama , Infecções por Coronavirus , Mastectomia , Estadiamento de Neoplasias , Pandemias , Pneumonia Viral , Medição de Risco , Tempo para o Tratamento , Betacoronavirus , Neoplasias da Mama/cirurgia , COVID-19 , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Pneumonia Viral/epidemiologia , SARS-CoV-2
14.
Curr Oncol Rep ; 21(3): 25, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30806829

RESUMO

PURPOSE OF REVIEW: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+ MBC) as well as current controversies and evolving areas of research. RECENT FINDINGS: Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+ MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the field include whether all patients with HR+ MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+ MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Feminino , Humanos
16.
Cancer ; 123(3): 401-409, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27727457

RESUMO

BACKGROUND: In 2009, the US Preventive Services Task Force recommended that the decision to initiate screening mammography before age 50 years should be individualized. Herein, the authors examined whether health care providers are communicating regarding mammography decision making with women and whether communication is associated with screening behavior. METHODS: Data were drawn from the 2011 to 2014 Health Information National Trends Survey (HINTS). A total of 5915 female respondents aged ≥ 40 years who responded to the following question were included: "Has a doctor or other health professional ever told you that you could choose whether or not to have a mammogram?" We used logistic regression to generate odds ratios (ORs) and 95% confidence intervals (95% CIs) for predictors of provider communication and assessed whether provider communication was associated with mammography in the previous 2 years overall and stratified by age. RESULTS: Fewer than 50% of the women reported provider communication regarding mammogram choice. Women who reported provider communication were not found to be more likely to report no mammogram within the past 2 years (OR, 1.07; 95% CI, 0.87-1.31) compared with those who did not. When stratified by 10-year age group, provider communication was associated with a higher likelihood of no mammogram only among women age ≥70 years (OR, 1.64; 95% CI, 1.15-2.34), and was associated with a lower likelihood of no mammogram only among women aged 40 to 49 years (OR, 0.63; 95% CI, 0.43-0.92). CONCLUSIONS: Between 2011 and 2014, less than one-half of women received communication regarding mammogram choice despite recommendations from the US Preventive Services Task Force. Provider communication regarding mammogram choice can influence screening behavior, particularly for younger and older women. Cancer 2017;123:401-409. © 2016 American Cancer Society.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Mamografia , Programas de Rastreamento , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/patologia , Tomada de Decisões , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Fatores Socioeconômicos , Estados Unidos
17.
Oncologist ; 22(9): 1039-1048, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28706010

RESUMO

Aberrations of the cell cycle are pervasive in cancer, and selective cell cycle inhibition of cancer cells is a target of choice for a number of novel cancer therapeutics. Cyclin-dependent kinases (CDKs) are key regulatory enzymes that control cell cycle transitions and the commitment to cell division. Palbociclib and ribociclib are both orally active, highly selective reversible inhibitors of CDK4 and CDK6 that are approved by the U.S. Food and Drug Administration (FDA) for hormone receptor-positive metastatic breast cancer in combination with specific endocrine therapies. A third oral CDK4/6 inhibitor, abemaciclib, received Breakthrough Therapy designation status from the FDA and is also being developed in breast cancer. The most common adverse events associated with palbociclib and ribociclib are hematologic, particularly neutropenia. However, the neutropenia associated with CDK4/6 inhibitors is distinct from chemotherapy-induced neutropenia in that it is rapidly reversible, reflecting a cytostatic effect on neutrophil precursors in the bone marrow. Most hematologic abnormalities seen with CDK4/6 inhibitors are not complicated and are adequately managed with standard supportive care and dose adjustments when indicated. Cytopenias are less prevalent with abemaciclib, although fatigue and gastrointestinal toxicity is more common with this agent. This review focuses on the clinical management of potential toxicities and drug interactions seen with the use of CDK4/6 inhibitors in breast cancer, with a focus on palbociclib and ribociclib, and summarizes practical management strategies for an oncologist. IMPLICATIONS FOR PRACTICE: The emergence of modern cyclin-dependent kinase (CDK) inhibitors has changed the treatment paradigm for metastatic hormone receptor (HR)-positive breast cancer. Palbociclib, ribociclib, and abemaciclib are highly selective reversible inhibitors of CDK4 and CDK6. Palbociclib is U.S. Food and Drug Administration (FDA)-approved in the first- and second-line settings in combination with endocrine therapy for HR-positive metastatic breast cancer. Ribociclib is FDA-approved in the first-line setting. Abemaciclib has received FDA Breakthrough Therapy designation status. This review focuses on the clinical management of potential toxicities and drug interactions seen with the use of CDK4/6 inhibitors in breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Terapia de Alvo Molecular/efeitos adversos , Neutropenia/epidemiologia , Inibidores de Proteínas Quinases/farmacologia , Aminopiridinas/farmacologia , Benzimidazóis/farmacologia , Ensaios Clínicos como Assunto , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Interações Medicamentosas , Feminino , Humanos , Terapia de Alvo Molecular/métodos , Neutropenia/induzido quimicamente , Piperazinas/farmacologia , Purinas/farmacologia , Piridinas/farmacologia
19.
Expert Rev Anticancer Ther ; 24(6): 397-405, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642015

RESUMO

INTRODUCTION: Estrogen receptor positive (ER+) breast cancer is the most common breast cancer subtype, and therapeutic management relies primarily on inhibiting ER signaling. In the metastatic setting, ER signaling is typically targeted by selective estrogen receptor degraders (SERDs) or aromatase inhibitors (AIs), the latter of which prevent estrogen production. Activating ESR1 mutations are among the most common emergent breast cancer mutations and confer resistance to AIs. AREAS COVERED: Until 2023, fulvestrant was the only approved SERD; fulvestrant is administered intramuscularly, and in some cases may also have limited efficacy in the setting of certain ESR1 mutations. In 2023, the first oral SERD, elacestrant, was approved for use in ESR1-mutated, ER+/HER2- advanced breast cancer and represents a new class of therapeutic options. While the initial approval was as monotherapy, ongoing studies are evaluating elacestrant (as well as other oral SERDs) in combination with other therapies including CDK4/6 inhibitors and PI3K inhibitors, which parallels the current combination uses of fulvestrant. EXPERT OPINION: Elacestrant's recent approval sheds light on the use of biomarkers such as ESR1 to gauge a tumor's endocrine sensitivity. Ongoing therapeutic and correlative biomarker studies will offer new insight and expanding treatment options for patients with advanced breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Administração Oral , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/administração & dosagem , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Animais , Mutação , Fulvestranto/administração & dosagem , Fulvestranto/farmacologia , Resistencia a Medicamentos Antineoplásicos , Receptores de Estrogênio/metabolismo , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos
20.
J Am Coll Surg ; 238(3): 303-311, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38047578

RESUMO

BACKGROUND: Patients with ERBB2 (HER2)-positive breast cancer experience high pathologic complete response (pCR) rates after standard neoadjuvant anti-HER2 systemic therapy. We examined axillary pathologic nodal response to neoadjuvant dual HER2-targeted therapy alone, based on breast pathologic response, in a multi-institution clinical trial. STUDY DESIGN: Patients with HER2-positive breast cancer were enrolled to a phase II single-arm trial, which administered 6 cycles of neoadjuvant trastuzumab emtansine (T-DM1) plus pertuzumab. Rates of pathologic nodal disease (ypN) in patients who were clinically node-negative (cN0) and node-positive (cN1) were analyzed, by residual breast disease (pCR and residual cancer burden [RCB] I to III). RESULTS: One hundred fifty-eight patients completed preoperative treatment and proceeded to surgery. Of 92 patients who were cN0, 48 (52.2%) and 10 (10.9%) experienced breast pCR and RCB I, respectively. Of these, 100% were ypN0. Of 34 with RCB II to III, 26 (76.5%) were ypN0. Of 30 patients who were cN1 with breast pCR, 100% were ypN0; of the 12 patients who were cN1 with RCB I, 66.7% were ypN0; and of the 24 patients who were cN1 with RCB II to III, 25% were ypN0. ypN0 rates were significantly different between patients who did and did not experience a pCR, in both cN0 (p = 0.002) and cN1 (p < 0.001) subgroups. CONCLUSIONS: Patients with HER2-positive breast cancer treated with dual HER2-targeted therapy who experienced a breast pCR or RCB I response were frequently ypN0. These findings support future trials considering omission of axillary surgical staging for patients with HER2-positive breast cancer in neoadjuvant trials of active HER2-targeted regimens, particularly if they experience breast pCR or RCB I.


Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Receptor ErbB-2/uso terapêutico , Ado-Trastuzumab Emtansina/uso terapêutico
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