The management of TNBC is difficult since the disease is characterized by rapid growth, frequent nodal metastases, and a high risk of recurrence. In older adults, who account for 10% of patients with TNBC, treatment is further complicated by the presence of comorbidities, poor nutritional status, functional impairment, worsening organ function, and limited social support. These factors can predispose to a higher rate of chemotherapy-related toxicities, especially in frail and vulnerable older adults. Further, this segment is underrepresented in clinical trials, leaving a paucity of knowledge in how to adequately manage this population.
The Young International Society of Geriatric Oncology (YSIOG), which is comprised of junior members of the SIOG, published a review paper addressing specific considerations for assessing older patients with TNBC and summarizing information on the use of systemic treatments in this age group.
The group warned that relying on age and performance status can lead to either overtreatment or undertreatment of BC in older adults, referencing the International Society of Geriatric Oncology and American Society of Clinical Oncology. YSIOG called for the use of comprehensive geriatric assessment—the gold standard to assess frailty—prior to developing individualized treatment plans. Several chemotherapy-toxicity risk prediction models are available and include the Chemotherapy Risk Assessment Scale for High-Age Patients and the Cancer and Aging Research Group (CARG). These tools consider patient-, tumor-, and treatment-related factors; laboratory values; and geriatric assessment variables.
The CARG-Breast Cancer (CARG-BC), a newly validated model to predict grades 3 through 5 chemotherapy-induced toxicity in patients aged 65 years or older with early-stage disease, was found to be superior to the Karnofsky Performance Status Scale. The CARG-BC score is based on BC stage, planned use of anthracyclines, planned treatment duration, hemoglobin level, liver function status, fall history in the past 6 months, ability to walk more than 1 mile, and ability to handle a crisis.
The article discusses the use of neoadjuvant and adjuvant chemotherapy in early TNBC and chemotherapy and immunotherapy in advanced disease in older adults. While optimal neoadjuvant chemotherapy for TNBC in older adults is still not clearly established since this population has been excluded from clinical trials, the sequential use of anthracycline and taxanes may be considered in carefully selected, fit individuals with high-risk disease. The use of platinums may be beneficial in patients with BRCA mutations.
Other treatment regimen options include the use of poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors. While adjuvant chemotherapy is recommended for TNBC patients with tumors measuring greater than 5 mm and/or with pathologically involved lymph nodes based on the National Comprehensive Cancer Network and St. Gallen guidelines, it is not considered standard treatment in all patients aged 70 years or older.
Nonetheless, studies have shown that older women with TNBC treated with adjuvant therapy have improved overall survival compared with those who did not receive therapy. Adjuvant chemotherapeutic agents include doxorubicin-cisplatin, docetaxel-cyclophosphamide, and cyclophosphamide/methotrexate/fluorouracil, as well as capecitabine and olaparib (a PARP inhibitor)—although data are limited.
In advanced TNBC, the use of chemotherapy is palliative and typically involves the sequential use of a single chemotherapeutic agent including anthracyclines, taxanes, capecitabine, gemcitabine, eribulin, vinorelbine, ixabepilone, and cyclophosphamide. The choice for second- or third-line therapy is even less clear and may include the use of sacituzumab. Immunotherapy with pembrolizumab has shown some promise. In those with BRCA mutations, a PARP inhibitor or platinum-based therapy should be considered.
The paper also discusses the use of genetic testing in older patients with TNBC with a focus on BRCA, ATM, BRIP1, CHEK2, PALB2, RAD51F, and RAD51C genes. While this is still an emerging area of research, the authors caution to not exclude older TNBC patients from clinical trials as these studies may identify candidates for specific treatment recommendations and risk-reducing strategies.
As the proportion of persons aged 65 years and older continues to increase, this paper serves as a valuable resource for pharmacists caring for older adults with TNBC.
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