Management of hormone receptor–positive, human epidermal growth factor 2–negative metastatic breast cancer

Mouabbi, Jason; Osborne, C. Kent; Schiff, Rachel; Rimawi, Mothaffar F.

doi:10.1007/s10549-021-06383-5

Cited by 13 publications

(11 citation statements)

References 96 publications

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“…Another important mechanism is the alteration of the phosphatidylinositol 3-kinase (PI3K)/ AKT/mammalian target of the rapamycin (mTOR) pathway, which is known to be vital in mBC cell growth and drives ET resistance. Drugs targeting PI3K and mTOR are currently used in clinical practice in patients who experience disease progression on CDK4/ 6is plus ET 20 .…”

Section: Introductionmentioning

confidence: 99%

Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies

et al. 2022

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The addition of targeted therapies (TT) to endocrine therapy (ET) has improved the outcomes of patients with HR-positive, HER2-negative metastatic breast cancer (mBC). However, it is unknown whether patients with invasive lobular carcinoma (ILC) or mixed invasive ductal and lobular carcinoma (mixed) histologies experience the same magnitude of benefit from this therapy as those with invasive ductal carcinoma (IDC). We aim to determine whether patients with IDC, ILC, and mixed HR+/HER2− mBC derive similar benefit from the addition of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is), mammalian target of rapamycin inhibitor (mTORi), and phosphoinositide 3-kinase inhibitor (PI3Ki) to ET in HR+/HER2− mBC. We conducted an observational, population-based investigation using data from the MD Anderson prospectively collected database. We conducted a histology-based analysis of progression-free survival (PFS) and overall survival (OS) durations in 3784 patients with HR+/HER2− mBC who were treated with TT plus ET between January 1, 2010, and December 31, 2021. Out of the 3784 patients, 2975 were included in the final analysis. Of these, 2249 received CDK4/6is (81% IDC, 15% ILC, and 4% mixed), 1027 received everolimus (82% IDC, 14% ILC, and 4% mixed) and 49 received alpelisib (81% IDC and 19% ILC). The addition of targeted therapy to ET did not result in statistically significant differences in PFS or OS duration among patients with IDC, ILC, and mixed HR+/HER2− mBC. We concluded that for patients with HR+/HER2− mBC, the addition of TT to ET leads to a similar magnitude of benefit, irrespective of histology.

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Section: Introductionmentioning

confidence: 99%

Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies

et al. 2022

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“…Hormone receptor (HR)-positive, ERBB2 (formerly HER2 or HER2/neu)-negative (OMIM 164870) metastatic breast cancer (mBC) is the most common subtype of mBCs, seen in approximately 60% of patients. 1 Historically, these tumors were treated with endocrine therapy (ET). 2 However, the development of targeted therapies (TTs), such as the cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), the mammalian target of rapamycin inhibitor everolimus, and the phosphoinositide 3-kinase inhibitor alpelisib, and their combination with ET have transformed the management of such tumors.…”

Section: Introductionmentioning

confidence: 99%

“…2 However, the development of targeted therapies (TTs), such as the cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), the mammalian target of rapamycin inhibitor everolimus, and the phosphoinositide 3-kinase inhibitor alpelisib, and their combination with ET have transformed the management of such tumors. 1 Until recently, patients with HR-positive, ERBB2-negative breast cancer have been treated with ET and TT until their disease becomes hormone refractory, and at that point, they start sequential single-agent chemotherapies. 1 The 2022 American Society of Clinical Oncology guidelines have changed this paradigm with the introduction of 2 antibody-drug conjugates to the field of HR-positive mBC: trastuzumab deruxtecan 3,4 and sacituzumab govitecan.…”

Section: Introductionmentioning

confidence: 99%

“…1 Until recently, patients with HR-positive, ERBB2-negative breast cancer have been treated with ET and TT until their disease becomes hormone refractory, and at that point, they start sequential single-agent chemotherapies. 1 The 2022 American Society of Clinical Oncology guidelines have changed this paradigm with the introduction of 2 antibody-drug conjugates to the field of HR-positive mBC: trastuzumab deruxtecan 3,4 and sacituzumab govitecan. 5,6 The DESTINY-Breast04 (Trastuzumab Deruxtecan [DS-8201a] vs Investigator's Choice for HER2-Low Breast Cancer That Has Spread or Cannot Be Surgically Removed) trial showed that when treated with trastuzumab deruxtecan, patients with mBC that expresses low levels of ERBB2 had significantly improved outcomes compared with standard-of-care therapies.…”

Section: Introductionmentioning

confidence: 99%

“…Hormone receptor (HR)–positive, ERBB2 (formerly HER2 or HER2 / neu )–negative (OMIM 164870) metastatic breast cancer (mBC) is the most common subtype of mBCs, seen in approximately 60% of patients . Historically, these tumors were treated with endocrine therapy (ET) .…”

Section: Introductionmentioning

confidence: 99%

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Survival Outcomes in Patients With Hormone Receptor–Positive Metastatic Breast Cancer With Low or No ERBB2 Expression Treated With Targeted Therapies Plus Endocrine Therapy

et al. 2023

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ImportanceApproximately 45% to 60% of hormone receptor (HR)–positive metastatic breast cancer (mBC) shows a low-level expression of ERBB2. Low ERBB2 expression is defined as ERBB2 immunohistochemical expression of 1+ or 2+ with a negative ERBB2 amplification by in situ hybridization. The efficacy of the antibody-drug conjugate trastuzumab deruxtecan in low-ERBB2, HR-positive mBC has been practice changing. However, there are conflicting data on the prognostic value of low ERBB2 expression in HR-positive mBC and whether low ERBB2 expression is a separate entity.ObjectiveTo examine whether outcomes differ by immunohistochemical analysis for patients with HR-positive mBC with low ERBB2 expression vs those without ERBB2 expression when treated with targeted therapy (TT) plus endocrine therapy (ET).Design, Setting, and ParticipantsThis single-institution cohort study used prospectively collected electronic data from the MD Anderson Cancer Center for patients with a diagnosis of HR-positive mBC treated with ET in combination with a TT (cyclin-dependent kinase 4/6 inhibitors [CDK4/6is], everolimus, or alpelisib) between January 1, 2010, and December 31, 2021.ExposureHR-positive mBC with either low or no ERBB2 expression.Main Outcome and MeasuresThe main outcomes were median progression-free survival and overall survival. Data on demographic characteristics, estrogen and progesterone receptor status, ERBB2 status, histologic subtype, menopausal status, treatment duration, and survival status were collected.ResultsA total of 1585 women (median [range] age, 51 [24-92] years) were included in the study. Of these women, 1013 (63.9%) had mBC with low ERBB2 expression and 572 (36.1%) had mBC with no ERBB2 expression. A total of 1084 (68.4%) were treated with a CDK4/6i (912 patients were treated in the first line and 172 were treated in the second line); 475 (30.0%) received everolimus and 26 (1.6%) received alpelisib. In the patients who received a first-line CDK4/6i, 618 (67.8%) received an aromatase inhibitor as their ET backbone and 265 (29.1%) received fulvestrant. With a median follow-up time of 17.9 months (range, 1-111 months), progression-free survival and overall survival were not statistically different between the patients with low and no ERBB2 expression treated with TT plus ET.Conclusions and RelevanceIn this cohort study of patients with HR-positive mBC treated with TT plus ET, low ERBB2 expression did not have a significant association with prognosis.

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Invasive lobular carcinoma: an understudied emergent subtype of breast cancer

Mouabbi

Hassan

Lim

et al. 2022

Breast Cancer Res Treat

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Management of hormone receptor–positive, human epidermal growth factor 2–negative metastatic breast cancer

Cited by 13 publications

References 96 publications

Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies

Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies

Survival Outcomes in Patients With Hormone Receptor–Positive Metastatic Breast Cancer With Low or No ERBB2 Expression Treated With Targeted Therapies Plus Endocrine Therapy

Invasive lobular carcinoma: an understudied emergent subtype of breast cancer

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