Combined endocrine and targeted therapy in luminal breast cancer

Goldner, Marcelle; Pandolfi, Natasha Carvalho; Maciel, Débora Alves; Lima, Juliana Bezerra Medeiros de; Sanches, Solange Moraes; Pondé, Noam

doi:10.1080/14737140.2021.1960160

Cited by 14 publications

(12 citation statements)

References 125 publications

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“…The lack of adjuvant palbociclib efficacy does not preclude further integration of CDK4/6i into the breast cancer treatment algorithm. In addition to new combinations being currently investigated in various breast cancer subtypes, 43 translational science will help to better understand unique tissue and/or serum biomarkers 44 that may predict individual benefit or resistance 45 for each of the approved CDK4/6 inhibitors to guide optimal patient selection and treatment combinations. 46 The sizable trans-PALLAS biorepository containing both tumor tissue and serial plasma specimens together with the planned clinical long-term follow-up of patients will serve as an excellent resource to support such important research.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)

Gnant

Dueck

Frantal

et al. 2022

JCO

122

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PURPOSE Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor–positive breast cancer has not been confirmed. PATIENTS AND METHODS In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer–free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival. RESULTS Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial. CONCLUSION At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor–positive breast cancer.

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Section: Discussionmentioning

confidence: 99%

Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)

Gnant

Dueck

Frantal

et al. 2022

JCO

122

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“…Most ERα+ breast cancer patients will receive 5 years of first-line adjuvant hormone therapy, often in conjunction with CDK4/6 (palbociclib/ribociclib/abemaciclib), mTORC1 (everolimus), or PI3K (alpelisib) inhibitors 7 . Aromatase inhibitors (AIs) are a common post-menopausal first-line therapy used to ablate estrogen levels via estradiol synthesis inhibition.…”

Section: Introductionmentioning

confidence: 99%

Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells

et al. 2022

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Estrogen receptor alpha (ERα) is a ligand-dependent master transcriptional regulator and key driver of breast cancer pathology. Small molecule hormones and competitive antagonists favor unique ERα conformational ensembles that elicit ligand-specific transcriptional programs in breast cancer and other hormone-responsive tissues. By affecting disparate ligand binding domain structural features, unconventional ligand scaffolds can redirect ERα genomic binding patterns to engage novel therapeutic transcriptional programs. To improve our understanding of these ERα structure-transcriptional relationships, we develop a series of chemically unconventional antagonists based on the antiestrogens elacestrant and lasofoxifene. High-resolution x-ray co-crystal structures show that these molecules affect both classical and unique structural motifs within the ERα ligand binding pocket. They show moderately reduced antagonistic potencies on ERα genomic activities but are effective anti-proliferative agents in luminal breast cancer cells. Interestingly, they favor a 4-hydroxytamoxifen-like accumulation of ERα in breast cancer cells but lack uterotrophic activities in an endometrial cell line. Importantly, RNA sequencing shows that the lead molecules engage transcriptional pathways similar to the selective estrogen receptor degrader fulvestrant. This advance shows that fulvestrant-like genomic activities can be achieved without affecting ERα accumulation in breast cancer cells.

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“…According to four indicators of the expression levels of certain receptors (ER, PR, Her-2, and Ki-67), the molecular subtypes of breast cancer are classified into luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) -enriched and triple-negative (3)(4)(5). Generally, luminal types account for the majority (about 70%) of invasive breast cancers and respond well to endocrine therapy (6,7). The selection of targeted antibody therapy is a priority for HER2-enriched types (8).…”

Section: Introductionmentioning

confidence: 99%

Application of DCE-MRI radiomics signature analysis in differentiating molecular subtypes of luminal and non-luminal breast cancer

et al. 2023

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BackgroundThe goal of this study was to develop and validate a radiomics signature based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) preoperatively differentiating luminal and non-luminal molecular subtypes in patients with invasive breast cancer.MethodsOne hundred and thirty-five invasive breast cancer patients with luminal (n = 78) and non-luminal (n = 57) molecular subtypes were divided into training set (n = 95) and testing set (n = 40) in a 7:3 ratio. Demographics and MRI radiological features were used to construct clinical risk factors. Radiomics signature was constructed by extracting radiomics features from the second phase of DCE-MRI images and radiomics score (rad-score) was calculated. Finally, the prediction performance was evaluated in terms of calibration, discrimination, and clinical usefulness.ResultsMultivariate logistic regression analysis showed that no clinical risk factors were independent predictors of luminal and non-luminal molecular subtypes in invasive breast cancer patients. Meanwhile, the radiomics signature showed good discrimination in the training set (AUC, 0.86; 95% CI, 0.78–0.93) and the testing set (AUC, 0.80; 95% CI, 0.65–0.95).ConclusionThe DCE-MRI radiomics signature is a promising tool to discrimination luminal and non-luminal molecular subtypes in invasive breast cancer patients preoperatively and noninvasively.

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Combined endocrine and targeted therapy in luminal breast cancer

Cited by 14 publications

References 125 publications

Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)

Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)

Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells

Application of DCE-MRI radiomics signature analysis in differentiating molecular subtypes of luminal and non-luminal breast cancer

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