What is the treatment and prognosis for invasive breast carcinoma that is estrogen receptor (ER) positive, progesterone receptor (PR) positive, with unknown human epidermal growth factor receptor 2 (HER2) status, and a Ki-67 index indicating moderate proliferation?

From the Guidelines

The treatment for breast invasive carcinoma that is estrogen and progesterone receptor positive with unknown HER2 status and a Ki67 index of 22% should involve a multidisciplinary approach, including surgery, adjuvant endocrine therapy, and consideration of chemotherapy and HER2 testing.

Key Considerations

• Surgery is the primary treatment, either breast-conserving surgery (lumpectomy) with radiation therapy or mastectomy depending on tumor size, location, and patient preference.
• Adjuvant endocrine therapy is recommended for 5-10 years with medications such as tamoxifen (20mg daily) for premenopausal women or aromatase inhibitors (anastrozole 1mg daily, letrozole 2.5mg daily, or exemestane 25mg daily) for postmenopausal women, as supported by guidelines from the National Comprehensive Cancer Network 1.
• With a Ki67 index of 22%, which indicates intermediate to high proliferation, chemotherapy is often recommended before or after surgery, with common regimens including AC-T (Adriamycin/Cyclophosphamide followed by Taxol) or TC (Taxotere/Cyclophosphamide).
• HER2 testing should be completed to determine if anti-HER2 therapy is needed, as the presence of HER2 positivity may influence treatment decisions, including the potential use of pertuzumab, trastuzumab, or other targeted therapies 1.

Prognosis and Follow-Up

• The prognosis for hormone receptor-positive breast cancer is generally favorable, with 5-year survival rates of 90% or higher for early-stage disease.
• Regular follow-up with oncology is essential, including physical exams every 3-6 months for the first 3 years, then every 6-12 months for years 4-5, and annually thereafter, along with annual mammography.

Treatment Recommendations

• Adjuvant endocrine therapy should be initiated as soon as possible after surgery, with the choice of medication dependent on menopausal status and other individual factors.
• Chemotherapy and HER2 testing should be considered on a case-by-case basis, taking into account tumor characteristics, patient preferences, and overall health status.
• Treatment decisions should be made in consultation with a multidisciplinary team of healthcare professionals, including surgeons, medical oncologists, radiation oncologists, and other specialists as needed.

From the FDA Drug Label

Among 29,441 patients with ER positive or unknown breast cancer, 58% were entered into trials comparing tamoxifen to no adjuvant therapy and 42% were entered into trials comparing tamoxifen in combination with chemotherapy vs. the same chemotherapy alone. Among women with ER positive or unknown breast cancer and positive nodes who received about 5 years of treatment, overall survival at 10 years was 61.4% for tamoxifen vs. 50.5% for control (logrank 2p < 0.00001). The recurrence-free rate at 10 years was 59.7% for tamoxifen vs. 44.5% for control (logrank 2p < 0. 00001). Among women with ER positive or unknown breast cancer and negative nodes who received about 5 years of treatment, overall survival at 10 years was 78.9% for tamoxifen vs. 73.3% for control (logrank 2p < 0.00001). The recurrence-free rate at 10 years was 79.2% for tamoxifen vs. 64.3% for control (logrank 2p < 0. 00001).

The treatment for breast invasive carcinoma estrogen progesterone positive, unknown HER2, Ki67 index 22% may include tamoxifen as an adjuvant therapy.

• The prognosis is generally favorable with a 10-year overall survival rate of 61.4% to 78.9% and a recurrence-free rate of 59.7% to 79.2% for patients with ER positive or unknown breast cancer who received about 5 years of tamoxifen treatment 2.
• The benefit of tamoxifen is less clear for women with ER poor breast cancer.
• The effects of about 5 years of tamoxifen on recurrence and mortality were similar regardless of age and concurrent chemotherapy.
• There was no indication that doses greater than 20 mg per day were more effective.

From the Research

Treatment and Prognosis for Breast Invasive Carcinoma

• The treatment and prognosis for breast invasive carcinoma that is estrogen and progesterone positive, with unknown HER2 status, and a Ki67 index of 22% can be informed by several studies 3, 4, 5, 6, 7.
• Estrogen receptor positive and progesterone receptor positive tumors are generally associated with better survival outcomes compared to those that are estrogen receptor positive and progesterone receptor negative 3.
• The Ki67 index is a measure of cell proliferation, and a value of 22% is considered relatively high, which may indicate a more aggressive tumor 5, 6.
• Studies have shown that hormone blocking therapy can be effective in improving overall survival for patients with estrogen receptor positive and progesterone receptor positive tumors 3.
• However, the conversion of hormone receptor status, including estrogen and progesterone receptors, after neoadjuvant chemotherapy can have an impact on survival outcomes, and receptor status should be re-evaluated routinely before and after treatment to guide individualized treatment 6, 7.
• The HER2 status is also an important factor in determining treatment options, but in this case, it is unknown, and further testing would be needed to determine the best course of treatment.
• In terms of prognosis, patients with tumors that have a high Ki67 index, such as 22%, may have a poorer prognosis compared to those with lower Ki67 indices 6.

Impact of Neoadjuvant Chemotherapy

• Neoadjuvant chemotherapy can affect the status of estrogen receptor, progesterone receptor, and HER2/neu, and changes in receptor status can have an impact on survival outcomes 4, 6, 7.
• A study found that the conversion of estrogen receptor and progesterone receptor status after neoadjuvant chemotherapy was related to overall survival and disease-free survival, and patients whose receptor status was always positive had the best prognosis 6.
• Another study found that there was no statistically significant difference in estrogen receptor and HER2/neu expression between pre- and post-neoadjuvant chemotherapy specimens, but a statistically significant loss of progesterone receptor expression was noted between the two groups 7.

Ki67 Index and Prognosis

• The Ki67 index is a prognostic factor for breast cancer, and high Ki67 indices are associated with poorer prognosis 5, 6.
• A study found that patients whose Ki67 index was ≤20% persistently after neoadjuvant chemotherapy had the best survival, while those whose Ki67 index changed from ≤20% to >20% after neoadjuvant chemotherapy had the worst survival 6.