Real-World Analysis of Clinical and Demographic Characteristics, Treatment Patterns, and Outcomes in Predominantly Older Patients with HR+/HER2- Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

Introduction: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) is the most frequently diagnosed metastatic breast cancer (mBC) subtype. Combinations of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4 & 6is) improve outcomes compared with ET alone. The efficacy and safety of abemaciclib among patients with HR+/HER2- mBC has been demonstrated in the MONARCH clinical trials; however, there is a paucity of real-world evidence, particularly in older patients.

Adjuvant Abemaciclib Combined with Endocrine Therapy: Efficacy Results in monarchE Cohort 1.

The monarchE Cohort 1 patient population was enrolled based on high-risk clinicopathological features that can easily be identified as part of routine clinical breast cancer evaluation. Efficacy data from Cohort 1 demonstrate substantial evidence of benefit for adjuvant abemaciclib+ET in patients with HR+, HER2- early breast cancer at high risk of recurrence (ClinicalTrials.gov: NCT03155997 [monarchE]).

Population-based estimate for the correlation of the Oncotype Dx Breast Recurrence Score® result and Ki-67 IHC MIB-1 pharmDx in HR+, HER2-, node-positive early breast cancer.

Background: The United States Food and Drug Administration recently approved a Ki-67 immunohistochemistry (IHC) assay to identify patients with early breast cancer at high disease recurrence risk. The Oncotype Dx Breast Recurrence Score® assay has been validated in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) invasive breast cancer (IBC) to predict chemotherapy benefit and distant recurrence risk, regardless of nodal status. This study assessed the correlation between Recurrence Score® (RS) results and the Ki-67 IHC MIB-1 pharmDx assay.

Two Instrument Comparison of Reagents From a US FDA-Approved Assay for the Assessment of Ki-67 in High-Risk Early Breast Cancer.

The objective of this study was to measure concordance of results obtained from the US Food and Drug Administration-approved Ki-67 immunohistochemistry MIB-1 pharmDx assay performed on the Dako Omnis automated staining instrument (Omnis) versus results produced from the assay reagents applied using an optimized protocol on the more widely available Autostainer Link 48 (ASL48) platform. Tissue sections obtained from 40 formalin-fixed paraffin-embedded breast carcinoma samples, with available Oncotype DX Breast Recurrence Score (RS) results, were stained. Three certified pathologists scored slides at 3 timepoints, totaling 360 observations for each instrument (N=720 total) using the approved scoring approach.

First-line therapy for treatment-naive patients with advanced/metastatic renal cell carcinoma: a systematic review of published randomized controlled trials.

In the recent years, a number of targeted therapies have been approved for first-line treatment of patients with metastatic renal cell carcinoma. A systematic review was conducted to assess the clinical efficacy, safety and effect of all first-line treatments evaluated to date on health-related quality of life (HRQoL). A systematic search of Embase, Cochrane and MEDLINE databases was performed to identify randomized controlled trials (1980-2015) evaluating any targeted therapy/immunotherapy against placebo or any other targeted intervention/immunotherapy in treatment-naive patients with metastatic renal cell carcinoma.

Dose-dependent change in biomarkers during neoadjuvant endocrine therapy with fulvestrant: results from NEWEST, a randomized Phase II study.

NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors) is the first study to compare biological and clinical activity of fulvestrant 500 versus 250 mg in the neoadjuvant breast cancer setting. We hypothesized that fulvestrant 500 mg may be superior to 250 mg in blocking estrogen receptor (ER) signaling and growth. A multicenter, randomized, open-label, Phase II study was performed to compare fulvestrant 500 mg (500 mg/month plus 500 mg on day 14 of month 1) versus fulvestrant 250 mg/month for 16 weeks prior to surgery in postmenopausal women with ER+ locally advanced breast cancer.

Fulvestrant revisited: efficacy and safety of the 500-mg dose.

Postmenopausal women with hormone receptor-positive advanced breast cancer are candidates for endocrine therapy. As the disease will eventually progress in most patients, it is important to investigate agents with novel modes of action to reduce the likelihood of treatment cross-resistance. Fulvestrant is an estrogen receptor antagonist with no known agonist effects that has been shown to be as effective as anastrozole following failure on tamoxifen, at the approved dose of 250 mg/mo.

Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer.

Purpose: We compared fulvestrant 500 mg regimen with the approved dose of fulvestrant 250 mg per month for treatment of postmenopausal women with estrogen receptor-positive advanced breast cancer who experienced progression after prior endocrine therapy.

Patients And Methods: Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) is a double-blind, parallel-group, multicenter, phase III study. Patients were randomly assigned to fulvestrant 500 mg (500 mg intramuscularly [IM] on day 0, then 500 mg IM on days 14 and 28 and every 28 days thereafter) or 250 mg every 28 days.

Aromatase inhibitor-induced carpal tunnel syndrome: results from the ATAC trial.

Purpose: Carpal tunnel syndrome (CTS) is a condition in which the median nerve is compressed, leading to pain and muscle weakness in the fingers and hand. Aromatase inhibitors lead to profound estrogen suppression and may be expected to increase the risk of CTS in postmenopausal women receiving adjuvant therapy for early breast cancer.

Patients And Methods: The current analyses were based on the 100-month median follow-up data in postmenopausal women in the two monotherapy arms (anastrozole, n = 3,092; tamoxifen, n = 3,094).

Pharmacokinetic profile of the fulvestrant loading dose regimen in postmenopausal women with hormone receptor-positive advanced breast cancer.

Purpose: Fulvestrant is at least as effective as anastrozole in the treatment of postmenopausal women with advanced breast cancer whose disease has previously progressed or recurred on antiestrogen therapy. Pharmacokinetic data have shown that, at the approved dose (250 mg/month), it takes approximately 3-6 months for fulvestrant to reach steady-state levels. Theoretically, a more rapid attainment of steady state might reduce the number of early progressions.

Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis.

Background: Joint symptoms (eg, arthralgia and arthritis) are a well-known side-effect of aromatase inhibitors. Low oestrogen concentrations and postmenopausal status are associated with the development of these symptoms. Chemotherapy can also induce joint symptoms, but tamoxifen seems to have little effect on their incidence.

Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT.

Purpose: The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR+) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure.

Materials And Methods: Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR+ advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI.

Occult primary breast carcinoma presenting as axillary lymphadenopathy.

Background: The objective of this study was to review the need for radiotherapy or not in patients with occult primary breast cancer presenting with axillary metastases treated with breast conservation usually with no surgery to the breast.

Methods: From 1975 to 2001, 58 patients were treated with axillary lymphadenopathy from a cryptic primary breast carcinoma. After clinical and radiological assessment, 29 patients retained a diagnosis of occult primary breast carcinoma.