What are the risk groups for choosing hormone therapy in a patient with stage 1 breast cancer treated with Radiation Therapy (RT) and hormone therapy?

From the Guidelines

When choosing hormone therapy for a stage 1 breast cancer patient treated with Radiation Therapy (RT), high-risk premenopausal patients with HR-positive tumors, characterized by young age, high-grade tumor, and lymph node involvement, should be considered for ovarian function suppression (OFS) with a gonadotropin-releasing hormone (GnRH) agonist, such as goserelin or leuprolide, in addition to endocrine therapy. The decision to add OFS to endocrine therapy should be based on a balanced discussion of the risks and benefits, including the potential side effects of premature menopause 1.

Risk Stratification

The primary risk stratification depends on hormone receptor status, with treatment only recommended for estrogen receptor (ER) and/or progesterone receptor (PR) positive tumors. Key risk factors that warrant consideration of OFS include:

• Young age
• High-grade tumor
• Lymph node involvement
• High risk of recurrence, as determined by factors such as tumor size, lymphovascular invasion, and Ki-67 proliferation index

Treatment Options

For premenopausal women, tamoxifen 20mg daily for 5-10 years is standard, with extended therapy for higher-risk patients. OFS with a GnRH agonist may be added for higher-risk premenopausal women, with a recommended duration of at least 2 years, and up to 5 years, based on the results of the TEXT-SOFT trials and the ASTRRA trial 1. For postmenopausal women, aromatase inhibitors (anastrozole 1mg, letrozole 2.5mg, or exemestane 25mg daily) are preferred for 5-10 years, though tamoxifen remains an option.

Considerations

Treatment selection must also consider comorbidities, as tamoxifen increases thromboembolism and endometrial cancer risk, while aromatase inhibitors can cause bone density loss and arthralgias. Genomic assays like Oncotype DX can help quantify recurrence risk and guide treatment decisions. Ultimately, the choice of hormone therapy should be individualized based on the patient's specific risk factors, medical history, and preferences.

From the FDA Drug Label

Table 5 Demographic and Baseline Tumor Characteristics from the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)

Parameter | Exemestane (N = 2352) | Tamoxifen (N = 2372) Age (years): Median age (range) | 63.0 (38.0 – 96.0) | 63.0 (31.0 – 90.0) ... Nodal status, n (%): | Negative | 1217 (51.7) | 1228 (51.8) Positive | 1051 (44.7) | 1044 (44. 0) ... Receptor status*, n (%): | ER and PgR Positive | 1331 (56.6) | 1319 (55.6) ER Positive and PgR Negative/Unknown | 677 (28.8) | 692 (29.2) ... Tumor Size, n (%): | ≤ 0.5 cm | 58 (2.5) | 46 (1.9)

0.5 – 1.0 cm | 315 (13. 4) | 302 (12.7) ...

The risk groups for choosing hormone therapy in a patient with stage 1 breast cancer treated with Radiation Therapy (RT) and hormone therapy are:

• Nodal status:
  • Negative
  • Positive (1–3,4–9, or >9 positive nodes)
• Receptor status:
  • ER and PgR Positive
  • ER Positive and PgR Negative/Unknown
  • ER Unknown and PgR Positive/Unknown
  • ER Negative and PgR Positive
  • ER Negative and PgR Negative/Unknown
• Tumor size:
  • ≤ 0.5 cm

  • 0.5 – 1.0 cm

  • 1.0 – 2 cm

  • 2.0 – 5.0 cm

  • 5.0 cm

• Tumor grade:
  • G1
  • G2
  • G3
  • G4
  • Unknown/Not Assessed/Not reported 2

From the Research

Risk Groups for Hormone Therapy in Stage 1 Breast Cancer

The decision to choose hormone therapy in patients with stage 1 breast cancer treated with Radiation Therapy (RT) and hormone therapy depends on various factors, including the risk of recurrence and the patient's hormone receptor status.

• Patients with hormone receptor-positive tumors are at a higher risk of recurrence and may benefit from extended endocrine therapy 3.
• The risk of breast cancer recurrence persists after 5 years and is cumulative and indefinite 3.
• Studies have shown that extended endocrine therapy can provide a disease-free survival benefit, especially in patients with high-risk features such as node-positive disease or high-grade tumors 4, 3.
• Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have been shown to be effective in reducing the risk of recurrence in postmenopausal women with hormone receptor-positive breast cancer 5, 6, 4.
• The choice of endocrine therapy and extended endocrine therapy should be individualized based on the patient's risk of recurrence, likely benefit of extended therapy, tolerability of current endocrine therapy, and patient preference 3.

Patient Selection for Extended Endocrine Therapy

Patients who may benefit from extended endocrine therapy include:

• Those with high-risk features such as node-positive disease or high-grade tumors 4, 3.
• Those who have completed 5 years of tamoxifen therapy and are at high risk of recurrence 4.
• Those who are postmenopausal and have hormone receptor-positive tumors 5, 6, 4.

Prognostic Tools for Patient Selection

Prognostic tools such as the Oncotype DX test and the PAM50 test can be used to assist with patient selection for extended endocrine therapy 3. These tools can help identify patients who are at high risk of recurrence and may benefit from extended therapy.