What Is the Optimal Endocrine Therapy for Postmenopausal Women With Hormone Receptor–Positive Early Breast Cancer?

2013 ◽  
Vol 31 (11) ◽  
pp. 1391-1397 ◽  
Author(s):  
Nadine Tung
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Recurrence Score ◽  
Prescription Medication ◽  
Left Breast ◽  
Hormone Receptor Positive ◽  
Er Positive ◽  
Epidermal Growth ◽  
Recent Diagnosis

A 56-year-old postmenopausal woman with a recent diagnosis of breast cancer was referred to discuss adjuvant therapy. Annual screening mammogram demonstrated a suspicious mass in the left breast. Ultrasound-guided core needle biopsy revealed an infiltrating ductal carcinoma that was estrogen receptor (ER) positive and progesterone receptor (PR) negative and lacked amplification of human epidermal growth factor receptor 2 (HER2; ie, HER2 negative). She underwent excision and sentinel node evaluation. Pathology demonstrated a 1.9-cm grade 2 invasive cancer without lymphatic vascular invasion; clean margins were obtained, and both sentinel nodes were free of cancer. The 21-gene recurrence score was 16. She has a body mass index (BMI) of 28.5 but is otherwise healthy; levothyroxine is the only prescription medication she takes. She experienced vaginal spotting 2 years earlier because of an endometrial polyp, which was resected. She exercises regularly and takes a calcium supplement with vitamin D. Bone density study performed 6 months earlier was normal other than mild osteopenia in the femoral neck (T score, −1.3). Radiation therapy is planned

scholarly journals Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

2021 ◽  
Vol 28 (1) ◽  
pp. 678-688
Author(s):  
Katie Mycock ◽  
Lin Zhan ◽  
Gavin Taylor-Stokes ◽  
Gary Milligan ◽  
Debanjali Mitra
Keyword(s):  
Breast Cancer ◽  
Real World ◽  
Medical Records ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Retrospective Chart Review ◽  
Hormone Receptor Positive ◽  
Kaplan Meier ◽  
Epidermal Growth

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.

scholarly journals Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy

Breast Cancer ◽  
2021 ◽  
Author(s):  
Kenichi Inoue ◽  
Norikazu Masuda ◽  
Hiroji Iwata ◽  
Masato Takahashi ◽  
Yoshinori Ito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Confidence Interval ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Phase 3 ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

Abstract Background This was a Japanese subpopulation analysis of MONARCH 2, a double-blind, randomized, placebo-controlled, phase 3 study of abemaciclib plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Methods Eligible women had progressed on (neo)adjuvant endocrine therapy (ET), ≤ 12 months from end of adjuvant ET, or on first-line ET for ABC, and had not received chemotherapy for ABC. Patients were randomized 2:1 to receive abemaciclib or placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), pharmacokinetics (PK), health-related quality of life (HRQoL), and safety. Results In Japan, 95 patients were randomized (abemaciclib, n = 64; placebo, n = 31). At final PFS analysis (February 14, 2017), median PFS was 21.2 and 14.3 months, respectively, in the abemaciclib and placebo groups (hazard ratio: 0.672; 95% confidence interval: 0.380–1.189). Abemaciclib had a higher objective response rate (37.5%) than placebo (12.9%). PK and safety profiles for Japanese patients were consistent with those of the overall population, without clinically meaningful differences across most HRQoL dimensions evaluated. The most frequent adverse events in the abemaciclib versus placebo groups were diarrhea (95.2 versus 25.8%), neutropenia (79.4 versus 0%), and leukopenia (66.7 versus 0%). At a second data cutoff (June 20, 2019), median OS was not reached with abemaciclib and 47.3 months with placebo (hazard ratio: 0.755; 95% confidence interval: 0.390–1.463). Conclusions Results of the Japanese subpopulation were consistent with the improved clinical outcomes and manageable safety profile observed in the overall population. Clinical trial registration NCT02107703; U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02107703.

Model Development of CDK4/6 Predicted Efficacy in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced or Metastatic Breast Cancer

2021 ◽  
pp. 758-767
Author(s):  
Jeremy Mason ◽  
Yutao Gong ◽  
Laleh Amiri-Kordestani ◽  
Suparna Wedam ◽  
Jennifer J. Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prediction Models ◽  
Area Under The Curve ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Tumor Characteristics ◽  
Average Area ◽  
Hormone Receptor Positive ◽  
The Us ◽  
Epidermal Growth

PURPOSE Three cyclin-dependent kinase 4/6 inhibitors (CDKIs) are approved by the US Food and Drug Administration for the treatment of patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced or metastatic breast cancer in combination with hormonal therapy (HT). We hypothesized that on an individual basis, efficacy outcomes and adverse event (AE) development can be predicted using baseline patient and tumor characteristics. METHODS Individual-level data from seven randomized controlled trials submitted to the US Food and Drug Administration for new or supplemental marketing applications of CDKIs were pooled. Progression-free survival (PFS), overall survival (OS), and AE prediction models were developed for specific treatment regimens (HT v HT plus CDKI). An individual's characteristics were used in all models simultaneously to create a group of predicted outcomes that are comparable across treatment settings. RESULTS Accuracy of the PFS and OS prediction models for HT were 66% and 64%, respectively, with the strongest predictors being menopausal status and therapy line. The corresponding AE prediction models resulted in an average area under the curve of 0.613. Accuracy of the PFS and OS prediction models for HT plus CDKI were 62% and 63%, respectively, with the strongest predictors being histologic grade for both. The corresponding AE prediction models resulted in an average area under the curve of 0.639. CONCLUSION This exploratory analysis demonstrated that models of efficacy outcomes and AE development can be developed using baseline patient and tumor characteristics. Comparison of paired models can inform treatment selection for individuals on the basis of the patient's personalized goals and concerns. Although use of CDKIs is standard of care in the first- or second-line setting, this model provides prognostic information that may inform individual treatment decisions.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers

2008 ◽  
Vol 26 (6) ◽  
pp. 897-906 ◽  
Author(s):  
Marta Guix ◽  
Nara de Matos Granja ◽  
Ingrid Meszoely ◽  
Theresa B. Adkins ◽  
Bobbye M. Wieman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Growth Factor Receptor ◽  
Preoperative Treatment ◽  
Breast Cancers ◽  
Tumor Cell Proliferation ◽  
Hormone Receptor Positive ◽  
Er Positive ◽  
Her 2

Purpose To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) –positive but not in human epidermal growth factor receptor 2 (HER-2) –positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor–positive cancers. Conclusion A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2–positive or triple-negative breast cancers.

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