Targeted Therapy for Premenopausal Women with HR+, HER2− Advanced Breast Cancer: Focus on Special Considerations and Latest Advances

Abstract

The incidence of advanced breast cancer in premenopausal women is increasing, and breast cancer in younger women is often more aggressive and has a worse prognosis compared with breast cancer in older women. Premenopausal women with hormone receptor-positive (HR) breast cancer are frequently under-represented in clinical trials, and treatment strategies in the premenopausal setting are usually extrapolated from data from postmenopausal patients, with the addition of ovarian function suppression to endocrine therapy in HR disease. However, the underlying biology of breast cancer in premenopausal women can be different from postmenopausal women, and treatment strategies should ideally be specifically tested in premenopausal patients. Recent phase III trials have now investigated cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in premenopausal patients with HR, HER2 advanced breast cancer: Palbociclib and abemaciclib have been tested in a subset of premenopausal patients in the PALOMA-3 and MONARCH-2 studies, and ribociclib has been tested in the phase III MONALEESA-7 trial, which was entirely dedicated to premenopausal women. This comprehensive review summarizes the differences in the biology of HR, HER2 breast cancer in the premenopausal population compared with the postmenopausal population; discusses special considerations for treatment of premenopausal women; and reviews the evidence from clinical trials investigating endocrine therapy, other targeted treatments, and ovarian function suppression in the HR, HER2 advanced breast cancer setting. .

Optimizing care for younger women with hormone receptor‐positive, HER2‐negative metastatic breast cancer

“…A delayed diagnosis can be due to a number of factors, including the absence of routine screening for healthy, average-risk young women; the presence of a low index of suspicion on the part of patients and/or their primary healthcare providers; and the denser nature of breast tissue in younger women, which makes it more difficult to detect breast cancer via mammography or ultrasound. 2,4,6,11 The tendency for breast cancer to be more aggressive in younger patients and so more difficult to treat than in older patients is consistent with evidence that breast cancer may be biologically different in younger women. 12,13 For example, at a molecular level, it is known that younger women are more likely to harbor germline BRCA1 or BRCA2 mutations than older individuals with the disease; 12,13 and, more recently, estrogen receptor-positive (ER + ) tumors from premenopausal patients have been found to be molecularly distinct from ER + tumors from postmenopausal patients, in terms of gene expression, DNA methylation, copy number and somatic mutation patterns.…”

“…Younger women are more likely to present with aggressive, higher-grade and more advanced-stage disease and tend to have poorer prognoses. [2][3][4][5][6][7] Due to their age, younger women with breast cancer also often have to contend with a variety of other challenges or concerns (e.g. the development of treatment-related menopausal symptoms and/or loss of fertility; concerns about the impact of their diagnosis and treatment on relationships, their ability to parent young children and/or continue to work), which may necessitate additional assessment, monitoring and support.…”

“…the development of treatment-related menopausal symptoms and/or loss of fertility; concerns about the impact of their diagnosis and treatment on relationships, their ability to parent young children and/or continue to work), which may necessitate additional assessment, monitoring and support. 2,3,5,6,[8][9][10][11] The fact that younger patients are likely to have more advanced disease at diagnosis may be partly due to later diagnoses. A delayed diagnosis can be due to a number of factors, including the absence of routine screening for healthy, average-risk young women; the presence of a low index of suspicion on the part of patients and/or their primary healthcare providers; and the denser nature of breast tissue in younger women, which makes it more difficult to detect breast cancer via mammography or ultrasound.…”

Machilin D, a Lignin Derived from Saururus chinensis, Suppresses Breast Cancer Stem Cells and Inhibits NF-κB Signaling

“…Breast tumors are the most frequently diagnosed malignancy in breast tissue and are a major cause of cancer-related death in women [35]. Although the mortality of breast cancer has been stabilized, the morbidity is increasing, especially in premenopausal women with a poor prognosis and unfavourable molecular subtypes compared with postmenopausal patients older than 40 years [36]. According to the biological characteristics of the tumor, including stage, grade and genetic status, major treatments, such as surgical resection, chemotherapy and radiotherapy, are selected to increase the survival rate of breast cancer patients [37,38].…”

A population-based comparison of treatment patterns, resource utilization, and costs by cancer stage for Ontario patients with hormone receptor-positive/HER2-negative breast cancer

“…Further research on guideline adherence would be valuable for this subgroup since indications for upfront chemotherapy in HR+ disease are rare [9]. It was not until the latter part of our study that mTOR and cyclin-dependent kinase (CDK) 4/6 inhibitors were introduced into clinical practice [8,9,[44][45][46]. This is reflected in the low usage rates for our metastatic cohort; 4.9% and 2.1%, respectively, the latter of which is expected to increase over time.…”