Beyond 5 years: enduring risk of recurrence in oestrogen receptor-positive breast cancer

Richman, Juliet; Dowsett, Mitch

doi:10.1038/s41571-018-0145-5

Cited by 73 publications

(67 citation statements)

References 89 publications

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“…Endocrine therapy is the mainstay of treatment in both local and metastatic HR+ tumors and includes ER inhibition by either ER modulators (i.e., tamoxifen (TAM)), ER degraders (i.e., fulvestrant), or estrogen deprivation by aromatase inhibitors (AI). Approximately 40% of patients diagnosed with local/loco-regional HR+ breast cancer treated with endocrine therapy will eventually develop recurrent disease [2,3]. Recurrence events can be loco-regional metastases (about 3-8% of cases [4][5][6]), distant metastases, or both.…”

Section: Introductionmentioning

confidence: 99%

ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis

et al. 2020

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Background: Emerging mutations in the ESR1 gene that encodes for the estrogen receptor (ER) are associated with resistance to endocrine therapy. ESR1 mutations rarely exist in primary tumors (~1%) but are relatively common (10-50%) in metastatic, endocrine therapy-resistant cancers and are associated with a shorter progression-free survival. Little is known about the incidence and clinical implication of these mutations in early recurrence events, such as local recurrences or newly diagnosed metastatic disease. Methods:We collected 130 archival tumor samples from 103 breast cancer patients treated with endocrine therapy prior to their local/metastatic recurrence. The cohort consisted of 41 patients having at least 1 sample from local/ loco-regional recurrence and 62 patients with metastatic disease (of whom 41 newly diagnosed and 28 with advanced disease). The 5 most common ESR1 hotspot mutations (D538G, L536R, Y537S/N/C) were analyzed either by targeted sequencing or by droplet digital PCR. Progression-free survival (PFS), disease-free survival (DFS), and distant recurrence-free survival (DRFS) were statistically tested by Kaplan-Meier analysis.Results: The prevalence of ESR1 mutations was 5/41 (12%) in newly diagnosed metastatic patients and 5/28 (18%) for advanced metastases, detected at allele frequency > 1%. All mutations in advanced metastases were detected in patients previously treated with both tamoxifen (TAM) and aromatase inhibitors (AI). However, in newly diagnosed metastatic patients, 4/5 mutations occurred in patients treated with TAM alone. PFS on AI treatment in metastatic patients was significantly shorter for ESR1 mutation carriers (p = 0.017). In the local recurrence cohort, ESR1 mutations were identified in 15/41 (36%) patients but only 4/41 (10%) were detected at allele frequency > 1%. Again, most mutations (3/4) were detected under TAM monotherapy. Notably, 1 patient developed ESR1 mutation while on neoadjuvant endocrine therapy. DFS and DRFS were significantly shorter (p = 0.04 and p = 0.017, respectively) in patients that had ESR1 mutations (> 1%) in their loco-regional recurrence tumor.

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Section: Introductionmentioning

confidence: 99%

ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis

et al. 2020

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“…Breast cancer, and especially estrogen receptor (ER) positive breast cancer, has the ability to recur many years after primary diagnosis. 7 Recently, a meta-analysis of 88 trials involving >60,000 women with estrogen receptor positive tumors, reported that distant breast cancer recurrences continued to occur at a steady rate for at least 20 years after diagnosis. The risk of distant recurrence was associated with the original tumor size and lymph node status, whereby the risk increased from 13% for TNM (tumor node metastasis) stage T1N0 to 41% for T2N4-9 stage.…”

Section: Introductionmentioning

confidence: 99%

<p>Validation of an Algorithm to Ascertain Late Breast Cancer Recurrence Using Danish Medical Registries</p>

Pedersen

Öztürk

Mellemkjær

et al. 2020

CLEP

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We constructed an algorithm to ascertain late breast cancer recurrence-which we define as breast cancer that recurs 10 years or more after primary diagnosis (excluding contralateral breast cancers)-using Danish nationwide medical registries. We used clinical information recorded in medical records as a reference standard. Methods: Using the Danish Breast Cancer Group clinical database, we ascertained data on 21,134 women who survived recurrence-free 10 years or more after incident stage I-III breast cancer diagnosed in 1987-2004. We used a combination of Danish registries to construct the algorithm-the Danish National Patient Registry for information on diagnostic, therapeutic and procedural codes; and cancer diagnoses from the Danish Pathology Registry, the Danish Cancer Registry and the Contralateral Breast Cancer database. To estimate the positive predictive value (PPV), we selected 105 patients who, according to our algorithm, had late recurrence diagnosed at Aarhus University Hospital. To estimate the sensitivity, specificity and negative predictive value (NPV), we selected 114 patients diagnosed with primary breast cancer at Aalborg University Hospital. We abstracted clinical information on late recurrence for patients with medical record-confirmed late recurrence at Aarhus University Hospital. Results: Our algorithm had a PPV of late recurrence of 85.7% (95% CI: 77.5-91.3%), a sensitivity of 100.0% (95% CI, 39.8-100.0%), a specificity of 97.3 (95% CI, 92.2-99.4) and a NPV of 100% (95% CI, 96.6-100.0%). Conclusion: Our algorithm for late recurrence showed a moderate to high PPV and high sensitivity, specificity and negative predictive value. The algorithm could be an important tool for future studies of late breast cancer recurrence.

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“…8 In the UK, the phenotype of around threequarters of all breast cancers is characterised by the presence of ERα. 3,9,10 Therefore, ERα is a key receptor biomarker whose status plays a pivotal role in the classification of breast cancer subtypes, since its overexpression is related to increased proliferation and metastasis in breast cancer 11 which makes it an important marker for prediction of the likelihood of a patient developing metastatic disease. 12 Therefore, the accurate assess-ment of ERα status is essential for diagnosis and treatment decision making for breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of estrogen receptor alpha (ERα) expression in breast cancer cells and effect of drug treatment using targeted nanoparticles and SERS

Kapara

Brunton

Graham

et al. 2020

Analyst

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Beyond 5 years: enduring risk of recurrence in oestrogen receptor-positive breast cancer

Cited by 73 publications

References 89 publications

ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis

ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis

<p>Validation of an Algorithm to Ascertain Late Breast Cancer Recurrence Using Danish Medical Registries</p>

Characterisation of estrogen receptor alpha (ERα) expression in breast cancer cells and effect of drug treatment using targeted nanoparticles and SERS

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