Erin Roesch, MD
The utilization of neoadjuvant chemotherapy is increasing, and is considered standard of care for the majority of patients with HER2-positive and triple-negative breast cancer subtypes. A significant benefit of neoadjuvant systemic therapy is assessment of the tumor biology via chemotherapy response, which has prognostic implications and additionally can help tailor therapy in the adjuvant setting. In the era of precision medicine, de-escalation strategies are considered to provide patients with efficacious treatment and spare toxicity. Tasoulis et al assessed the accuracy of image-guided biopsy after neoadjuvant therapy to predict residual disease, and found a false negative rate (FNR) of 3.2% and negative predictive value (NPV) of 97.4% when the residual imaging abnormality was 2cm or smaller with a minimum of 6 vacuum-assisted biopsies performed. They also demonstrated a FNR of 4.2% and NPV of 97.2% in the subgroup of patients with ERBB2-positive and triple-negative subtypes, those most likely to achieve a pathologic complete response. These findings suggest that local therapy de-escalation may be a relevant strategy for those patients who have excellent responses to neoadjuvant chemotherapy.
Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) have historically been, and still are, considered important prognostic and predictive factors. Beyond these, the role of genomic assays in breast cancer is evolving, and the 21-gene recurrence score is a valuable prognostic tool to assess chemotherapy benefit in women with early-stage ER-positive, HER2-negative breast cancer. Precision medicine in oncology strives to identify and apply an individualized approach to cancer care based on strong scientific data. Zhang and colleagues demonstrated the prognostic ability of an 8 DNA repair-related gene signature that was constructed from gene expression profiles from over 1,000 women diagnosed with breast cancer. These genes have roles in ER-mediated transactivation, DNA damage repair and cell adhesion processes. Additionally, Kudela et al showed that microRNAs (mRNAs), which are small RNAs that regulate gene expression, are able to classify intrinsic breast cancer subtype, play a role in endocrine resistance, and may also enhance the function of predictive models such as the 21-gene recurrence score (Kudela). Ongoing research in the field of tumor genomics will help advance the field of personalized treatment for breast cancer.
Erin Roesch, MD
The Cleveland Clinic
References:
Killelea BK, Yang VQ, Wang SY, Hayse B, Mougalian S, Horowitz NR, Chagpar AB, Pusztai L, Lannin DR. Racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer: results from the National Cancer Data Base. J Clin Oncol. 2015;33:4267-76.
Heil J, Schaefgen B, Sinn P, Harcos A, Gomez C, Stieber A, Hennings A, Schuetz F, Sohn C, Schneeweiss A, Golatta M. Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. Br J Cancer . 2015;113:1565-70.
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111-21.
Emmadi R, Canestrari E, Arbieva ZH, Mu W, Dai Y, Frasor J, Wiley E. Correlative analysis of miRNA expression and Oncotype Dx Recurrence Score in estrogen receptor positive breast carcinomas. PLoS One. 2015;10:e0145346.