The Evolving Complexity of Treating Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer: Special Considerations in Older Breast Cancer Patients—Part I: Early-Stage Disease

The median age for breast cancer diagnosis is 62 years, but a disproportionate number of patients are over the age of 75 years and the majority of those have hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative cancers. This review provides a logical algorithm to guide providers through the many complicated issues involved in adjuvant systemic therapy decisions in older patients with hormone receptor-positive, HER2-negative breast cancer. For this subtype of breast cancer, the mainstay of treatment is surgery and adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor (AI). Adjuvant chemotherapy is added to the treatment regimen when the benefits of treatment are deemed to outweigh the risks, making the risk–benefit discussion particularly important in older women. Traditional tools for cancer risk assessment and genomic expression profiles (GEPs) are under-utilized in older patients, but yield equally useful information about cancer prognosis as they do in younger patients. Additionally, there are tools that estimate life-limiting toxicity risk from chemotherapy and life expectancy, which are both important issues in the risk–benefit discussion. For very low-risk cancers, such as non-invasive and small lymph node (LN)-negative cancers, the benefits of any adjuvant therapy is likely outweighed by the risks, but endocrine therapy might be considered to prevent future new breast cancers. For invasive tumors that are > 5 mm (T1b or larger) or involve LNs, adjuvant endocrine therapy is recommended. Generally, AIs should be included, though tamoxifen is effective and should be offered when AIs are not tolerated. Bone-preserving agents and high-dose vitamin D are options to preserve bone density or treat osteoporosis, especially in older women who are taking AIs. Where the risk-reducing benefit from adjuvant chemotherapy outweighs the toxicity risk, adjuvant chemotherapy should be considered. Adjuvant chemotherapy has similar benefits in older and younger patients and standard regimens are preferred. Several exciting clinic trials are underway and have included older patients, including those adding molecularly targeted agents, cyclin-dependent kinase (CDK) 4/6 inhibitors and everolimus, to endocrine therapy in the adjuvant setting. The high incidence of breast cancer in older women should drive us to design clinical trials for this population and emphasize their inclusion in ongoing trials as much as possible.