Should patients older than 75 years with node-positive, hormone receptor-positive breast cancer receive adjuvant chemotherapy?

From the Guidelines

Patients older than 75 with node-positive, hormone-positive breast cancer should not automatically be denied adjuvant chemotherapy, but rather, the decision should be individualized based on their overall health status, functional status, and tumor biology. When considering adjuvant chemotherapy for this population, it is essential to weigh the potential benefits against the increased risks of toxicity, including myelosuppression, cardiotoxicity, neuropathy, and cognitive decline 1.

Key Considerations

• Comprehensive geriatric assessment is crucial to evaluate functional status, comorbidities, cognitive function, and social support before initiating treatment.
• The biological characteristics of the tumor, such as the presence of multiple positive lymph nodes, high-grade tumors, or high genomic risk scores, play a significant role in determining the potential benefit of chemotherapy.
• Endocrine therapy alone, such as an aromatase inhibitor or tamoxifen for 5-10 years, plus possible CDK4/6 inhibitors, may be sufficient for many patients in this age group, avoiding the risks associated with chemotherapy 1.
• The decision to administer adjuvant chemotherapy should be based on a shared decision-making process between the clinical team and the patient, taking into account the patient's preferences, values, and quality of life.

Treatment Options

• Dose-reduced TC (docetaxel 75mg/m² and cyclophosphamide 600mg/m² every 3 weeks for 4 cycles) or AC (doxorubicin 60mg/m² and cyclophosphamide 600mg/m² every 3 weeks for 4 cycles) are common regimens used in this setting.
• The optimal duration of adjuvant endocrine therapy is still a topic of debate, but guidelines suggest that women with node-positive breast cancer should be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine treatment 1.

Recent Guidelines

• The 2024 NCCN guidelines suggest that HR-positive, HER2-negative breast cancer patients with a high risk of recurrence may benefit from adjuvant chemotherapy, but the decision should be individualized based on tumor biology and patient characteristics 1.
• The 2019 ASCO guideline update recommends that postmenopausal women with hormone receptor-positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen 1.

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. The effects of about 5 years of tamoxifen on recurrence and mortality were similar regardless of age and concurrent chemotherapy. Two studies (Hubay and NSABP B-09) demonstrated an improved disease-free survival following radical or modified radical mastectomy in postmenopausal women or women 50 years of age or older with surgically curable breast cancer with positive axillary nodes when tamoxifen was added to adjuvant cytotoxic chemotherapy

The decision to give adjuvant chemotherapy to patients older than 75 with node positive hormone positive breast cancer should be made on a case-by-case basis.

• Age is not a contraindication for adjuvant chemotherapy, but comorbidities and performance status should be considered.
• The benefits of chemotherapy in this population are not clearly established, and the risks of toxicity should be carefully weighed.
• Hormone receptor status is an important factor in determining the benefit of adjuvant therapy, and tamoxifen has been shown to be effective in reducing recurrence and mortality in patients with hormone receptor-positive breast cancer 2.
• Concurrent chemotherapy may be considered in addition to tamoxifen for patients with node-positive disease, but the decision should be individualized based on the patient's overall health and tumor characteristics.

From the Research

Adjuvant Chemotherapy for Node-Positive Hormone Receptor-Positive Breast Cancer in Patients Over 75

• The decision to administer adjuvant chemotherapy to patients over 75 with node-positive hormone receptor-positive breast cancer should be made on a case-by-case basis, considering factors such as overall health, tumor characteristics, and patient preferences 3, 4.
• Studies have shown that adjuvant chemotherapy can be beneficial for some patients with node-positive hormone receptor-positive breast cancer, particularly those with a higher risk of recurrence 3, 5.
• However, other studies have found that adjuvant chemotherapy may not be associated with improved overall survival in elderly patients (over 70 years old) with early-stage, hormone receptor-positive, HER-2-negative breast cancer 4.
• The 21-gene recurrence score assay (RS) has been used to predict the benefit of adjuvant chemotherapy in hormone receptor-positive, HER2-negative breast cancer patients, but its use in node-positive patients is still being studied 3.
• Clinicians should be cautious when considering omission of adjuvant chemotherapy in patients ≤ 70 years with HR+, HER2-, N1 tumors and a RS 12-25, at least until the results of the anticipated RxPONDER trial become available 3.
• The PAM50 risk of recurrence score and intrinsic subtype can identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared 5.