From the Guidelines
The newest treatments for estrogen-positive, progesterone-positive breast cancer include CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) combined with hormone therapy as first-line treatment for metastatic disease, as recommended by the most recent guidelines 1. These medications block cell division and significantly improve progression-free survival.
Key Treatment Options
- Standard hormone therapies remain important, including:
- Aromatase inhibitors (letrozole, anastrozole, exemestane)
- Selective estrogen receptor modulators (tamoxifen)
- Selective estrogen receptor degraders (fulvestrant)
- For HER2-positive cases, targeted therapies like trastuzumab are added.
- PI3K inhibitors (alpelisib) are effective for patients with PIK3CA mutations.
- Immunotherapy with pembrolizumab may benefit some patients, particularly those with high PD-L1 expression.
- PARP inhibitors (olaparib, talazoparib) show promise for patients with BRCA mutations.
Treatment Selection and Monitoring
Treatment selection depends on disease stage, prior therapies, menopausal status, and genetic profile, as outlined in the guidelines 1. Side effects vary by medication class but may include fatigue, bone loss, joint pain, and cardiac issues. Regular monitoring through imaging and blood tests is essential to assess treatment response, with treatment given until there is unequivocal evidence of disease progression 1. The use of combined endocrine therapy and chemotherapy is not recommended, and patients should be encouraged to consider enrolling in clinical trials 1.
From the FDA Drug Label
14 CLINICAL STUDIES 14. 1 Updated Adjuvant Treatment of Early Breast Cancer
In a multicenter study (BIG 1-98, NCT00004205) enrolling over 8,000 postmenopausal women with resected, receptor-positive early breast cancer, one of the following treatments was randomized in a double-blind manner: Option 1: Tamoxifen for 5 years Letrozole for 5 years Tamoxifen for 2 years followed by Letrozole for 3 years Letrozole for 2 years followed by tamoxifen for 3 years The study in the adjuvant setting, BIG 1-98, was designed to answer two primary questions: whether letrozole for 5 years was superior to Tamoxifen for 5 years (Primary Core Analysis) and whether switching endocrine treatments at 2 years was superior to continuing the same agent for a total of 5 years (Sequential Treatments Analysis). Letrozole was superior to tamoxifen in all endpoints except overall survival and contralateral breast cancer [e.g., DFS: hazard ratio, HR 0.79; 95% CI (0.68,0.92); P=0.002; SDFS: HR 0.83; 95% CI (0.70,0.97); TDM: HR 0.73; 95% CI (0.60,0.88); OS: HR 0.86; 95% CI (0.70,1.06).
The newest treatments for estrogen-positive progesterone-positive breast cancer include:
- Letrozole for 5 years, which has been shown to be superior to tamoxifen in disease-free survival (DFS), systemic disease-free survival (SDFS), and time to distant metastasis (TDM) 2.
- Tamoxifen is still an option, but letrozole has been found to be more effective in certain endpoints 2. It's essential to note that the choice of treatment should be based on individual patient factors and discussion with a healthcare provider.
From the Research
Newest Treatments for Estrogen Positive Progesterone Positive Breast Cancer
- The newest treatments for estrogen positive progesterone positive breast cancer include hormone blocking therapy, endocrine therapy, and combination therapy with aromatase inhibitors (AI) and cyclin-dependent kinase (CDK)4/6 inhibitors 3.
- Studies have shown that hormone blocking therapy is associated with increased overall survival for up to 10 years of follow-up in patients with ER+/PR- tumors, although the benefit may last for years after completion of the course 4.
- Endocrine therapy is recommended as the first-line treatment for hormone receptor-positive, HER2-negative metastatic breast cancer, except in cases of visceral crisis, where chemotherapy is preferred 5.
- Combination therapy with AI and CDK4/6 inhibitors has been shown to significantly improve progression-free survival, objective response rate, and disease control rate compared to AI monotherapy, but with increased toxicities 3.
- Fulvestrant 500 mg monotherapy has also been shown to significantly prolong progression-free survival compared to AI monotherapy 3.
- The American Society of Clinical Oncology/College of American Pathologists recommends ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose 6.
Treatment Options
- Hormone blocking therapy: associated with increased overall survival for up to 10 years of follow-up in patients with ER+/PR- tumors 4.
- Endocrine therapy: recommended as the first-line treatment for hormone receptor-positive, HER2-negative metastatic breast cancer 5.
- Combination therapy with AI and CDK4/6 inhibitors: significantly improves progression-free survival, objective response rate, and disease control rate compared to AI monotherapy, but with increased toxicities 3.
- Fulvestrant 500 mg monotherapy: significantly prolongs progression-free survival compared to AI monotherapy 3.
Testing and Diagnosis
- ER testing of invasive breast cancers by validated immunohistochemistry is recommended as the standard for predicting which patients may benefit from endocrine therapy 6.
- Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive, while samples with < 1% or 0% of tumor cell nuclei are immunoreactive should be considered ER negative 6.
- PgR testing is used primarily for prognostic purposes in the setting of an ER-positive cancer 6.