Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool.
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ABSTRACT:
SUBMITTER: Chia YH
PROVIDER: S-EPMC2966629 | biostudies-literature | 2010 Sep
REPOSITORIES: biostudies-literature
Publications
Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool.
Chia Y H YH Ellis M J MJ Ma C X CX
British journal of cancer 20100810 6
Neoadjuvant endocrine therapy has been increasingly employed in clinical practice to improve surgical options for postmenopausal women with bulky hormone receptor-positive breast cancer. Recent studies indicate that tumour response in this setting may predict long-term outcome of patients on adjuvant endocrine therapy, which argues for its broader application in treating hormone receptor-positive disease. From the research perspective, neoadjuvant endocrine therapy provides a unique opportunity ...[more]
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Project description:Mature outcomes from adjuvant endocrine therapy trials in estrogen receptor-positive breast cancer have enabled comparisons with neoadjuvant clinical trials that have parallel randomizations of treatment in terms of the response of disseminated disease versus the local response within the breast. Imprecise end points, such as 'clinical response', have produced inconsistent results regarding the relationship between neoadjuvant and adjuvant endocrine therapy outcomes. However, the proliferation marker Ki-67, measured during neoadjuvant treatment, has predicted accurately and consistently the results of much larger studies in the adjuvant setting. In this Review, we summarize these trials and discuss the implications for the design of future adjuvant endocrine therapy trials. We conclude that there is sufficient evidence supporting the view that the degree of Ki-67 suppression is a reliable short-term surrogate for the adjuvant potential of endocrine drugs, at least in postmenopausal women. We propose that adjuvant endocrine therapy trials should only be conducted once adequately-powered neoadjuvant studies have indicated superior Ki-67 suppression in patients receiving experimental endocrine treatment versus the standard treatment.
| S-EPMC3518447 | biostudies-other
Project description:PurposePhysician treatment preferences for early stage, estrogen positive breast cancer (ER + BC) patients were evaluated during the initial surge of the COVID-19 pandemic in the US when neoadjuvant endocrine therapy (NET) was recommended to allow safe deferral of surgery.MethodsA validated electronic survey was administered May-June, 2020 to US medical oncologists (MO), radiation oncologists (RO), and surgeons (SO) involved in clinical trials organizations. Questions on NET use included practice patterns for locoregional management following NET.Results114 Physicians from 29 states completed the survey-42 (37%) MO, 14 (12%) RO, and 58 (51%) SO. Before COVID-19, most used NET 'rarely' (49/107, 46%) or 'sometimes' (36, 33%) for ER + BC. 46% would delay surgery 2 months without NET. The preferred NET regimen was tamoxifen for premenopausal and aromatase inhibitor for postmenopausal women. 53% planned short term NET until surgery could proceed. Most recommended omitting axillary lymph node dissection (ALND) for one micrometastatic node after 1, 2, or 3 months of NET (1 month, N = 56/93, 60%; 2 months, N = 54/92, 59%; 3 months, N = 48/90, 53%). With longer duration of NET, omission of ALND decreased, regardless of years in practice, percent of practice in BC, practice type, participation in multidisciplinary tumor board, or number of regional COVID-19 cases.ConclusionMore physicians preferred NET for ER + BC during the pandemic, compared with pre-pandemic times. As the duration of NET extended, more providers favored ALND in low volume metastatic axillary disease. The Covid-19 pandemic affected practice of ER + BC; it remains to be seen how this may impact outcomes.
| S-EPMC7921279 | biostudies-literature
Project description:Nowadays, neoadjuvant endocrine therapy is a clinically acceptable (and sometimes preferred) strategy in patients with operable estrogen receptor-positive (ER+) breast cancer. Despite the overall effectiveness of endocrine therapy in breast cancer in all settings, de novo (primary) and acquired (secondary) endocrine therapy resistance remains a major clinical problem. Neoadjuvant endocrine therapy trials for breast cancer are not only a great opportunity to determine which ER+ breast cancers can be treated without chemotherapy, but also a great strategy to develop insights into the biologic basis for the efficacy of estrogen-receptor-targeting agents, alone or in combination, in an effort to counteract resistance to endocrine therapy and discover actionable molecular targets that can be the focus of future drug discovery efforts and/or translational/clinical investigation in ER+ breast cancers.
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Project description:Luminal 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.
| S-EPMC4720494 | biostudies-literature
Project description:In locally advanced (LA) breast cancer (BC), neoadjuvant treatments have led to major achievements, which hold particular relevance in HER2-positive and triple-negative BC. Conversely, their role in hormone receptor positive (HR+), hormone epidermal growth factor 2 negative (HER2-) BC is still under debate, mainly due to the generally low rates of pathological complete response (pCR) and lower accuracy of pCR as predictors of long-term outcomes in this patient subset. While administration of neoadjuvant chemotherapy (NCT) in LA, HR+, HER2- BC patients is widely used in clinical practice, neoadjuvant endocrine therapy (NET) still retains an unfulfilled potential in the management of these subgroups, particularly in elderly and unfit patients. In addition, NET has gained a central role as a platform to test new drugs and predictive biomarkers in previously untreated patients. We herein present historical data regarding Tamoxifen and/or Aromatase Inhibitors and a debate on recent evidence regarding agents such as CDK4/6 and PI3K/mTOR inhibitors in the neoadjuvant setting. We also discuss key issues concerning the optimal treatment length, appropriate comparisons with NCT efficacy and use of NET in premenopausal patients.
| S-EPMC7278946 | biostudies-literature
Project description:Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced, or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.
| S-EPMC8196711 | biostudies-literature
Project description:The American College of Surgeons Oncology Group Z1031 trial demonstrated that neoadjuvant endocrine therapy (NET) increased breast-conserving surgery (BCS) rates for postmenopausal patients with clinical tumor stage 2-4c estrogen receptor-positive breast cancer. We evaluated national trends in NET use in relation to the conduct of the Z1031 trial and the impact of NET on the rates of BCS.Using the National Cancer Data Base (NCDB), we identified all cT2-4c hormone receptor (HR)-positive breast cancer patients age ?50 years from 2004 to 2012. The time intervals of pre-Z1031 (2004-2006), during Z1031 (2007-2009), and post-Z1031 (2010-2012) were examined, and adjusted analyses were performed using multivariable logistic regression.Of 77,272 patients, 2294 (3.0 %) received NET. Clinical T-stage distribution was 66,885 (86.6 %) for cT2, 7318 (9.5 %) for cT3, and 3069 (4.0 %) for cT4a-c. A small but statistically significant increase in NET use was noted, from 2.7 % pre-Z1031 to 3.2 % post-Z1031; the adjusted odds ratio (OR) for NET was 1.28 [95 % confidence interval (CI) 1.13-1.45; p < 0.001] for post-Z1031 versus pre-Z1031. NET use varied by clinical T stage, increasing from 1.8 % pre-Z1031 to 2.4 % post-Z1031 in cT2 patients (p < 0.001) and from 6.3 % pre-Z1031 to 7.4 % post-Z1031 in cT3 patients (p = 0.02). Patients receiving NET were more likely to undergo BCS compared with patients undergoing primary surgery (46.4 vs. 43.9 %; p = 0.02) with an adjusted OR of 1.60 (95 % CI 1.46-1.75; p < 0.001).NET use has increased slowly since the Z1031 trial; however, overall use remains low. NET significantly increased the rates of BCS in patients with HR-positive clinical T2-4c breast cancer. Clinicians should consider NET use for patients with HR-positive breast cancer interested in BCS.
| S-EPMC5437722 | biostudies-other
Project description:Importance:Estrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear. Objective:To evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer. Data Sources:Based on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015. Study Selection:Inclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n?=?20). Two authors independently analyzed the studies for inclusion. Data Extraction and Synthesis:Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model. Results:The analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50-2.35; P?=?.85; n?=?378), radiological response rate (OR, 1.38; 95% CI, 0.92-2.07; P?=?.12; n?=?378), and BCS rate (OR, 0.65; 95% CI, 0.41-1.03; P?=?.07; n?=?334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36-2.10; P?<?.001; n?=?1352), radiological response rate (OR, 1.49; 95% CI, 1.18-1.89; P?<?.001; n?=?1418), and BCS rate (OR, 1.62; 95% CI, 1.24-2.12; P?<?.001; n?=?918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04-2.43; P?=?.03; n?=?355), but not clinical response rate (OR, 0.76; 95% CI, 0.54-1.07; P?=?.11; n?=?537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%). Conclusions and Relevance:Neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer.
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Project description:Breast cancer is one of the most common malignant cancers affecting females. Estrogen receptor (ER)-positive breast cancer is responsive to endocrine therapy. Although current therapies offer favorable prospects for improving survival, the development of resistance remains a severe problem. In this study, we explored the resistance mechanisms of ER-positive breast cancer to neoadjuvant endocrine therapy. Microarray data of GSE87411 contained 109 pairs of samples from Z1031 trial, including untreated samples and post-treated samples with neoadjuvant aromatase inhibitor (AI) therapy. The differentially expressed genes (DEGs) were obtained from two different comparisons: untreated samples versus post-treated samples with AIs, and post-treated samples sensitive versus resistant to AIs. Multiple bioinformatic methods were applied to evaluate biological function, protein-protein network and potential binding between target protein and aromatase inhibitor. Then, regulation of gene expression, DNA methylation and clinicopathological factors of breast cancer were further analyzed with TCGA data. From GSE87411 dataset, 30 overlapped DEGs were identified. Cell division was found to be the main function of overlapped DEGs by functional enrichment and gene ontology (GO) analysis. RAD51 recombinase (RAD51), a key protein of homologous recombination, was detected to interact with BReast CAncer genes 2 (BRCA2). Moreover, according to the docking simulation, RAD51 might potentially bind to AIs. Overexpressed RAD51 was associated with hypermethylation of BRCA2, resistance to AIs and poor overall survival of patients with ER-positive breast cancer. Furthermore, RAD51 was found to be a better indicator than MKI67 for predicting resistance in neoadjuvant setting. The results indicated that methylation of BRCA2 led to incomplete suppression on RAD51, which caused an increased expression of RAD51, subsequently AI-resistance and poor prognosis in ER-positive breast cancer. RAD51 could be a new candidate used as a predicative marker and therapeutic target in neoadjuvant endocrine treatment.
| S-EPMC6736845 | biostudies-literature
Project description:BackgroundNeoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer.MethodsBased on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010-2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0).ResultsOf 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson-Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET.ConclusionsAlthough the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.
| S-EPMC8330206 | biostudies-literature