Endocrine Therapy for Postmenopausal Women with Hormone Receptor–Positive her2–Negative Advanced Breast Cancer after Progression or Recurrence on Nonsteroidal Aromatase Inhibitor Therapy: A Canadian Consensus Statement

Pritchard, KI; Gelmon, Karen A.; Rayson, Daniel; Provencher, Louise; Webster, Marc; McLeod, Donald S A; Verma, Sunil

doi:10.3747/co.20.1316

Cited by 23 publications

(22 citation statements)

References 25 publications

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“…Conversely, resistance to tamoxifen was not associated with a universal endocrine resistant phenotype, as suggested by the different drug-response profiles of HBCx22 TamR and HBCx34 TamR. This is consistent with clinical observations where patients resistant to a given class of drug may still benefit from alternate ET (21,22), while ER expression is generally highly conserved in distant metastases (23,24). Li and colleagues recently identified ESR1 mutations in metastases of advanced ER þ breast cancer (13).…”

Section: Discussionsupporting

confidence: 66%

“…We report here the analysis of four original hormono resistant models, obtained from two ER þ breast cancer PDX, which have been rendered resistant to multiple modalities of ET, thus mimicking common clinical settings (21). Multiple resistances emerged from a single tumor, when challenged with different treatments (tamoxifen and estrogen deprivation).…”

Section: Discussionmentioning

confidence: 99%

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Acquired Resistance to Endocrine Treatments Is Associated with Tumor-Specific Molecular Changes in Patient-Derived Luminal Breast Cancer Xenografts

Cottu¹,

Bièche

Assayag³

et al. 2014

Clinical Cancer Research

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Purpose: Patients with luminal breast cancer (LBC) often become endocrine resistant over time. We investigated the molecular changes associated with acquired hormonoresistances in patient-derived xenografts of LBC. Experimental Design: Two LBC xenografts (HBCx22 and HBCx34) were treated with different endocrine treatments (ET) to obtain xenografts with acquired resistances to tamoxifen (TamR) and ovariectomy (OvaR). PI3K pathway activation was analyzed by Western blot analysis and IHC and responses to ET combined to everolimus were investigated in vivo. Gene expression analyses were performed by RT-PCR and Affymetrix arrays. Results: HBCx22 TamR xenograft was cross-resistant to several hormonotherapies, whereas HBCx22 OvaR and HBCx34 TamR exhibited a treatment-specific resistance profile. PI3K pathway was similarly activated in parental and resistant xenografts but the addition of everolimus did not restore the response to tamoxifen in TamR xenografts. In contrast, the combination of fulvestrant and everolimus induced tumor regression in vivo in HBCx34 TamR, where we found a cross-talk between the estrogen receptor (ER) and PI3K pathways. Expression of several ER-controlled genes and ER coregulators was significantly changed in both TamR and OvaR tumors, indicating impaired ER transcriptional activity. Expression changes associated with hormonoresistance were both tumor and treatment specific and were enriched for genes involved in cell growth, cell death, and cell survival. Conclusions: PDX models of LBC with acquired resistance to endocrine therapies show a great diversity of resistance phenotype, associated with specific deregulations of ER-mediated gene transcription. These models offer a tool for developing anticancer therapies and to investigate the dynamics of resistance emerging during pharmacologic interventions. Clin Cancer Res; 20(16); 4314–25. ©2014 AACR.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Acquired Resistance to Endocrine Treatments Is Associated with Tumor-Specific Molecular Changes in Patient-Derived Luminal Breast Cancer Xenografts

Cottu¹,

Bièche

Assayag³

et al. 2014

Clinical Cancer Research

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“…It is estimated that 75% of all breast cancer patients are hormone receptor-positive (HR+) breast cancer, and therefore might benefit from endocrine treatment [1]. Endocrine therapy significantly reduced the risk of death among patients with HRpositive tumors compared to those with ER and PgR-negative tumors.…”

Section: Introductionmentioning

confidence: 99%

Extended adjuvant endocrine therapy in hormone-receptor positive early breast cancer: Current and future evidence

Blok

Derks

Hoeven

et al. 2015

Cancer Treatment Reviews

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“…Predictive biomarkers such as ER and human epidermal growth factor receptors (EGFR/HER2) have allowed for individualized treatment decisions and optimization of clinical benefit within defined BC subsets. Endocrine therapies (ET) that lower estrogen levels or inhibit the stimulatory activity of estrogen on ER‐positive BC cells are often preferred for postmenopausal women with advanced HR‐positive/HER2‐negative BC because of their highly favorable therapeutic index . Tamoxifen—as well as the aromatase inhibitors (AIs) anastrozole, letrozole, or exemestane—is used in both adjuvant and advanced settings , with recent evidence also supporting consideration of the selective estrogen receptor downregulator fulvestrant .…”

Section: Introductionmentioning

confidence: 99%

Enhancing Endocrine Therapy Combination Strategies for the Treatment of Postmenopausal HR+/HER2– Advanced Breast Cancer

et al. 2017

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Breast cancer (BC) is the most common malignancy in women worldwide, with approximately two-thirds having hormone receptor-positive (HR1) tumors. New endocrine therapy (ET) strategies include combining ET agents as well as adding inhibitors targeting growth factors, angiogenesis, the mechanistic target of rapamycin, phosphoinositide 3-kinase (PI3K), or cyclindependent kinase 4/6 to ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib plus letrozole as firstline therapy for HR1/HER2 advanced BC with special consideration for the former in ET-na€ ıve patients, as well as everolimus plus exemestane or palbociclib plus fulvestrant as second-line therapy with special consideration in select first-line patients. Although the safety profiles of these combinations are generally predictable and manageable, both everolimus and palbociclib are associated with an increased risk of potentially serious or early-onset toxicities requiring individualized a priori adverse event risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Although each of these combinations improves progression-free survival, none with the exception of anastrazole plus fulvestrant have demonstrated improved overall survival. PI3K catalytic-a mutations assessed from circulating tumor DNA represent the first potentially viable serum biomarker for the selection of ET combinations, and new data demonstrate the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis. Therapeutic ratios of select ET combinations support their use in first-and second-line settings, but optimal sequencing has yet to be determined. The Oncologist 2017;22:12-24 Implications for Practice: Emerging data show that new endocrine therapy (ET) combinations can improve progression-free and overall survival outcomes in patients with hormone receptor-positive, HER2-negative (HR1/HER2) advanced breast cancer. Level 1 evidence supports consideration of dual ET regimens, particularly in ET-na€ ıve patients, or palbociclib plus letrozole as first-line therapy, as well as the addition of mTOR or CDK4/6 inhibitors to established ET in the second-line setting and in select first-line patients. Some combinations are associated with increased risk of class-specific toxicities that will require individualized risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Recent data on a noninvasive biomarker assay that predicts response to a phosphoinositide 3-kinase inhibitor demonstrates the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis.

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Endocrine Therapy for Postmenopausal Women with Hormone Receptor–Positive her2–Negative Advanced Breast Cancer after Progression or Recurrence on Nonsteroidal Aromatase Inhibitor Therapy: A Canadian Consensus Statement

Cited by 23 publications

References 25 publications

Acquired Resistance to Endocrine Treatments Is Associated with Tumor-Specific Molecular Changes in Patient-Derived Luminal Breast Cancer Xenografts

Acquired Resistance to Endocrine Treatments Is Associated with Tumor-Specific Molecular Changes in Patient-Derived Luminal Breast Cancer Xenografts

Extended adjuvant endocrine therapy in hormone-receptor positive early breast cancer: Current and future evidence

Enhancing Endocrine Therapy Combination Strategies for the Treatment of Postmenopausal HR+/HER2– Advanced Breast Cancer

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