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Commentary: New treatments and management in breast cancer, December 2022

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Erin Roesch, MD

There have been significant advances in systemic therapies for and, as a result, improved survival outcomes for early-stage breast cancer. These include neoadjuvant immunotherapy and adjuvant capecitabine for triple-negative breast cancer, as well as the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib for high-risk hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer in the adjuvant setting.1,2 Despite therapeutic progress, a proportion of patients remain at elevated risk for future relapse. The phase 3 randomized OlympiA trial investigated 1 year of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib as adjuvant therapy for patients with pathogenic germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer. Among 1836 patients with a median follow-up of 3.5 years, the second interim analysis of overall survival (OS) demonstrated significant benefit with olaparib vs placebo (hazard ratio [HR] 0.68; P = .009; 4-year OS was 89.8% in the olaparib group and 86.4% in the placebo group). The invasive disease-free and distant disease-free survival benefits were maintained as well (absolute benefits of 7.3% and 7.4% at 4 years, respectively) (Geyer et al). With increasing treatment options for patients, decisions regarding agent choice and sequencing are becoming increasingly complex.

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.3

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.4

Additional References

  1. Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
  2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
  3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
  4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

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