Axillary Response in Patients Undergoing Neoadjuvant Endocrine Treatment for Node-Positive Breast Cancer: Systematic Literature Review and NCDB Analysis

Abstract

Background. Several studies have proven that neoadjuvant endocrine therapy (NET) has a similar beneficial therapeutic effect in estrogen-positive (ER ?) breast cancer (BC) with improved breast conservation rate in patients undergoing NET versus neoadjuvant chemotherapy (NAC). The impact of axillary complete pathologic response (pCR) is less clear. We evaluate the impact of NET on axillary downstaging and surgical management. Methods. Using the National Cancer Database (NCDB), we identified all patients with node positive (N ?), ER ? , HER 2-BC undergoing NET and performed a systemic review of literature using PRISMA guidelines. Results. The literature review identified 1479 clinically N ? patients in four studies, 148 of whom had axillary pCR (10.0%). In the two studies of patients with invasive lobular carcinoma (ILC), 7.8% (69/883) of clinically N ? patients had axillary pCR. The NCDB query identified 4580 female patients with clinically N ? ER ? HER 2-BC who underwent NET from 2010 to 2016 with mean age of 61.4 years. Patients who achieved a pCR were more likely to have N1 disease (p 0.008), moderately differentiated tumors (p 0.003), and ductal histology (p 0.04). There was no statistically significant difference in race, comorbidity score, education, income, hospital setting, or clinical tumor stage. Of the 4580 total patients, 663 (14.48%) had an axillary pCR (pN0) after NET, and 3917 (85.52%) remained pN?. Conclusions. We found that patients who underwent NET for N ? disease had a higher axillary pCR than previously reported (10%) in smaller studies. Although NET is not a common treatment option for women with N ? ER ? HER 2-BC, it may be a suitable option for axillary downstaging, which is currently underutilized. In 2019, approximately 268,600 new cases of invasive breast cancer (IBC) and 48,100 cases of ductal carcinoma in situ (DCIS) were diagnosed among U.S. women, and more than 80% of breast cancers (BC) were diagnosed among women aged C 50 years. 1 Hormone receptor-positive (HR ?)/human epidermal growth factor receptor 2 (HER2)-negative BC is by far the most common subtype. 1 In patients with HR ? breast cancer, the innate exposure to endogenous estrogen results in dimerization of the estrogen receptor (ER) promoting estrogen gene transcription. 2 Multiple endocrine therapies have been developed for adjuvant use, such as selective ER downregulators, aromatase inhibitors (AIs), and luteinizing hormone releasing agonists. 3 The role of neoadjuvant endocrine therapy (NET) in the setting of HR ? breast cancer in the US is underutilized, typically being reserved for elderly patients,

Surgical Management of Axilla Following Neoadjuvant Endocrine Therapy

“…Similarly, Stafford et al studied patients from the NCDB during 2010–2016 with ER+/HER2– breast cancers treated with NET for > 30 days and reported a slightly higher axillary nodal pCR rate of 14.48% among 4580 patients staged as cN+. 27 They observed a higher likelihood of nodal pCR among patients with invasive ductal carcinoma, cN1 disease (75.9% of the study population), and grade II tumors. In that study, the duration of NET was unknown and patients with metastatic disease were included.…”

“…breast cancer, interest in this approach has been greatly accelerated by the COVID-19 pandemic and the rapid creation and adoption of guidelines for use of NET when surgery must be postponed. 4,18,27 Limitations of this study include its retrospective design without uniform selection criteria for NET, although patients were prospectively accrued. Additionally, longerterm follow-up will be important to further characterize FIG.…”

“… 6 , 9 While prior studies have shown low, albeit slowly increasing, uptake of NET for patients with ER+ breast cancer, interest in this approach has been greatly accelerated by the COVID-19 pandemic and the rapid creation and adoption of guidelines for use of NET when surgery must be postponed. 4 , 18 , 27 …”

The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment

“…A slight increase in these rates was observed by Rusz et al, reaching 13% node pCR in N+ patients after one year of NET with letrozole [ 31 ]. In a recent review, Stafford et al, after analyzing 4580 ER+ N+ breast cancers from the National Cancer Database, concluded that nodal pCR could be achieved in up to 14.5% of patients [ 32 ]. As reported by other authors, lobular breast cancer had a significantly lower percentage of nodal pCR when compared to ductal histologies (12.4% vs. 15.26%, p < 0.05) [ 32 , 33 ].…”

“…In a recent review, Stafford et al, after analyzing 4580 ER+ N+ breast cancers from the National Cancer Database, concluded that nodal pCR could be achieved in up to 14.5% of patients [ 32 ]. As reported by other authors, lobular breast cancer had a significantly lower percentage of nodal pCR when compared to ductal histologies (12.4% vs. 15.26%, p < 0.05) [ 32 , 33 ]. Longer treatment duration (>6 months) seems to increase the likelihood of nodal pCR [ 24 , 31 ].…”