What are the specific considerations when treating hormone receptor–positive disease in older patients?

1.

Elsevier ClinicalKey Clinical Overview

Treatment Patients aged 70 years or older with clinically node-negative, early-stage, hormone receptor–positive and HER2 - negative breast cancer do not require sentinel lymph node biopsy if treated with endocrine therapy For patients with hormone receptor–positive disease who cannot undergo surgery owing to limited life expectancy or comorbidities, primary endocrine therapy with either tamoxifen or an aromatase inhibitor can be used and can provide years of disease control even in the absence of surgery Recommendations regarding the treatment and subsequent surveillance of older patients with breast cancer have been published Adolescents and young adults Premenopausal patients risk permanent amenorrhea and infertility after chemotherapy Before treatment, arrange counseling on fertility preservation options (eg, cryopreservation of mature oocytes or embryos) Pregnancy should not occur during treatment with radiation therapy, systemic therapy, or endocrine therapy Temporary interruption of endocrine therapy to attempt pregnancy does not appear to increase short-term risk of breast cancer recurrence; however, long-term safety is unknown Contraceptive options to offer include intrauterine devices, barrier methods, or tubal ligation; hormone-based birth control, regardless of hormone receptor status of the cancer, is contraindicated Endocrine therapies frequently result in menopausal signs and symptoms in younger patients Management with lifestyle interventions, integrative therapies, and nonhormonal medications (eg, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin) is preferred Menopausal hormone therapy is contraindicated in patients with history of breast cancer Young women with invasive disease or pre-invasive lesions who are not high-risk mutation carriers do not have survival benefit from risk-reducing bilateral mastectomy

2.

Davidson, Nancy E. (2024). In Goldman-Cecil Medicine (pp. 1368). DOI: 10.1016/B978-0-323-93038-3.00183-0

Potential benefits include promotion of bone density and lowering of cholesterol. Tamoxifen is the preferred adjuvant endocrine therapy for premenopausal women and for men.Luteinizing hormone–releasing hormone (LHRH) agonists (e.g., leuprolide 3.75mg intramuscularly monthly) can temporarily and reversibly suppress ovarian function when used in combination with an aromatase inhibitor (e.g., exemestane 25mg daily) or tamoxifen (20 mg daily) and can improve disease-free survival in women who are premenopausal and are at sufficient risk for recurrence to warrant adjuvant chemotherapy.Administration of goserelin (a gonadotropin-releasing hormone agonist to protect ovarian function at 3.6 mg subcutaneously monthly) with chemotherapy may protect against permanent ovarian failure, thereby reducing the risk for early menopause and improving prospects for subsequent fertility.In postmenopausal women, the primary source of estrogen is the conversion of androgens synthesized by the adrenal glands to estrogen through the activity of CYP19 or aromatase in peripheral tissues such as mammary and adipose tissues. The aromatase inhibitors (anastrozole 1mg daily; letrozole 2.5mg daily; and exemestane 25 mg daily) specifically inhibit this conversion, thereby leading to further estrogen deprivation in older women. Multiple trials suggest that an aromatase inhibitor is preferred over tamoxifen in postmenopausal women and in premenopausal women who are receiving an LHRH agonist for estrogen receptor–positive breast cancer because these inhibitors reduce recurrence rates byabout 30% (proportionately) compared with tamoxifen.,Side effects include postmenopausal symptoms, osteoporosis, fractures, and arthralgias. Aromatase inhibitors are not useful for receptor-negative breast cancer, and they should not be used as monotherapy in premenopausal women or men with breast cancer.

3.

Food and Drug Administration (DailyMed).

Publish date: January 2, 2024.

Geriatric Use 8.5 Geriatric Use The median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64-65 years. About 1/3 of the patients were greater than or equal to 70 years old. In the first-line study, patients greater than or equal to 70 years of age experienced longer time to tumor progression and higher response rates than patients less than 70. For the extended adjuvant setting (MA-17), more than 5,100 postmenopausal women were enrolled in the clinical study. In total, 41% of patients were aged 65 years or older at enrollment, while 12% were 75 or older. In the extended adjuvant setting, no overall differences in safety or efficacy were observed between these older patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In the adjuvant setting (BIG 1-98), more than 8,000 postmenopausal women were enrolled in the clinical study. In total, 36% of patients were aged 65 years or older at enrollment, while 12% were 75 or older. More adverse reactions were generally reported in elderly patients irrespective of study treatment allocation. However, in comparison to tamoxifen, no overall differences with regard to the safety and efficacy profiles were observed between elderly patients and younger patients.

4.

Food and Drug Administration (DailyMed).

Publish date: January 4, 2024.

Geriatric Use 8.5 Geriatric Use The median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64-65 years. About 1/3 of the patients were greater than or equal to 70 years old. In the first-line study, patients greater than or equal to 70 years of age experienced longer time to tumor progression and higher response rates than patients less than 70. For the extended adjuvant setting (MA-17), more than 5,100 postmenopausal women were enrolled in the clinical study. In total, 41% of patients were aged 65 years or older at enrollment, while 12% were 75 or older. In the extended adjuvant setting, no overall differences in safety or efficacy were observed between these older patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In the adjuvant setting (BIG 1-98), more than 8,000 postmenopausal women were enrolled in the clinical study. In total, 36% of patients were aged 65 years or older at enrollment, while 12% were 75 or older. More adverse reactions were generally reported in elderly patients irrespective of study treatment allocation. However, in comparison to tamoxifen, no overall differences with regards to the safety and efficacy profiles were observed between elderly patients and younger patients.

5.

Food and Drug Administration (DailyMed).

Publish date: August 1, 2023.

Geriatric Use 8.5 Geriatric Use In studies 0030 and 0027, about 50% of patients were 65 or older. Patients ≥ 65 years of age had moderately better tumor response and time to tumor progression than patients < 65 years of age regardless of randomized treatment. In studies 0004 and 0005, 50% of patients were 65 or older. Response rates and time to progression were similar for the over 65 and younger patients. In the ATAC study, 45% of patients were 65 years of age or older. The efficacy of anastrozole tablets compared to tamoxifen in patients who were 65 years or older (N=1413 for anastrozole tablets and N=1410 for tamoxifen, the hazard ratio for disease-free survival was 0.93 [95% CI: 0.80, 1.08]) was less than efficacy observed in patients who were less than 65 years of age (N=1712 for anastrozole tablets and N=1706 for tamoxifen, the hazard ratio for disease-free survival was 0.79 [95% CI: 0.67, 0.94]). The pharmacokinetics of anastrozole are not affected by age.