What is the stage of a patient with T2 (tumor size), N1 (number of nearby lymph nodes involved), M0 (no distant metastasis) breast cancer that is estrogen receptor (ER) negative, progesterone receptor (PR) negative, and Her2/neu (human epidermal growth factor receptor 2) 3+ positive?

From the Guidelines

The treatment for T2N1M0 ER-PR-Her2neu 3+ breast cancer should involve a multimodal approach including surgery, systemic chemotherapy with an anthracycline and taxane-based combination, and targeted anti-HER2 therapy with trastuzumab and pertuzumab. This represents a tumor larger than 2 cm but not more than 5 cm (T2), with metastasis to 1-3 axillary lymph nodes (N1), and no distant metastasis (M0). The tumor is estrogen receptor negative (ER-), progesterone receptor negative (PR-), and HER2 positive (Her2neu 3+).

Key Considerations

• The standard chemotherapy regimen would include an anthracycline and taxane-based combination such as AC-T (Adriamycin/Cyclophosphamide followed by Taxol) or TCH (Taxotere, Carboplatin, Herceptin) 1.
• HER2-targeted therapy with trastuzumab (Herceptin) should be administered for a total of one year, often started concurrently with the taxane portion of chemotherapy 1.
• Pertuzumab may also be added to the regimen in high-risk cases, such as this one with ≥T2 or ≥N1, HER2-positive, early-stage breast cancer 1.
• Since the tumor is hormone receptor negative (ER-PR-), endocrine therapy is not indicated.
• Regular cardiac monitoring is essential during HER2-targeted therapy due to potential cardiotoxicity.

Treatment Approach

• Surgery: either breast-conserving surgery with radiation or mastectomy.
• Systemic chemotherapy: an anthracycline and taxane-based combination.
• Targeted anti-HER2 therapy: trastuzumab and pertuzumab. The HER2-positive status indicates overexpression of the HER2 protein, which promotes cancer cell growth but also provides a specific target for therapy, resulting in generally better outcomes with appropriate targeted treatment. The BCIRG 006 study demonstrated the efficacy of trastuzumab in combination with chemotherapy in patients with HER2-positive breast cancer, with a significant improvement in disease-free survival (DFS) and overall survival (OS) 1.

From the Research

T2N1M0 ER-PR-Her2neu 3+ Stage Breast Cancer

• The given stage of breast cancer is T2N1M0 ER-PR-Her2neu 3+, which indicates a tumor size of more than 2 cm but not more than 5 cm, with 1 to 3 axillary lymph nodes involved, no distant metastasis, and the tumor is estrogen receptor (ER) negative, progesterone receptor (PR) negative, and HER2 positive with a score of 3+ 2.
• For HER2-positive breast cancer, neoadjuvant therapy has become a standard clinical practice to downsize the tumor and increase the breast-conserving rate. The addition of trastuzumab to neoadjuvant chemotherapy roughly doubles the proportion of patients who achieve pathological complete response (pCR) 2.
• Targeting the HER2 pathway with trastuzumab and pertuzumab can further increase the pCR rate. Several studies have shown that neoadjuvant chemotherapy with trastuzumab plus pertuzumab is tolerable, increases the pCR rate compared with trastuzumab alone, and results in about 50-70% pCR rate 2.
• The KATHERINE trial demonstrated improved prognostic outcome for patients with residual disease after neoadjuvant therapy, with improved invasive disease-free survival (DFS) observed with the administration of postoperative trastuzumab emtansine in patients with HER2-positive breast cancer who had residual disease after neoadjuvant therapy 2.

Treatment Options

• There are various treatment options available for HER2-positive breast cancer, including neoadjuvant therapy, adjuvant therapy, and targeted therapy. The choice of treatment depends on the individual patient's characteristics, such as tumor size, lymph node involvement, and hormone receptor status 3, 4.
• For small, node-negative, HER2-positive breast cancer, the use of anti-HER2 treatment regimens is still controversial, with limited evidence available to support its use 3.
• The management of hormone receptor-positive, HER2-negative early breast cancer involves adjuvant endocrine therapy, specific endocrine therapy agents, and the duration of adjuvant endocrine therapy 4.
• Novel selective estrogen receptor degraders (SERDs) are being investigated as a promising therapeutic option for patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer 5.

Prognosis and Survival

• Patients with HER2-positive breast cancer who achieve pathological complete response (pCR) after neoadjuvant therapy have a better prognosis compared with those with residual disease 2.
• The 21-Gene recurrence score can predict the prognostic benefit of radiotherapy in patients aged 70 or older with T1N0 ER/PR+ HER2- breast cancer treated with breast-conserving surgery and endocrine therapy 6.
• The CAMBRIA-1 and CAMBRIA-2 phase III trials are investigating the efficacy of camizestrant, a novel SERD, versus standard endocrine therapy in patients with ER-positive/HER2-negative early breast cancer 5.