Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity

Jiaqiang Zhang,Ho-Min Chen,Szu-Yuan Wu,Chang-Yun Lu

doi:10.1001/jamanetworkopen.2021.1785

Jiaqiang Zhang, Ho-Min Chen + Show 2 more

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https://doi.org/10.1001/jamanetworkopen.2021.1785

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Abstract

Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer. To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT. This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020. NET vs NACT for IDC with strong HR positivity and ERBB2 negativity. The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments. A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P < .001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P = .002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P < .001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P < .001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P = .009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P = .005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P < .001). The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.

Highlights

The goal of neoadjuvant therapy is to improve surgical outcomes by inducing tumor shrinkage through effective systemic therapy; neoadjuvant therapy is useful for this because it can be initiated sooner than other therapies and treatment response can be assessed.[1]
In the multivariate Cox regression analyses, the adjusted hazard ratio for all-cause mortality among the neoadjuvant endocrine therapy (NET) cohort compared with the neoadjuvant chemotherapy (NACT) cohort was 2.67
The adjusted hazard ratio (aHR) for age were 1.13, 1.25, and 1.37 for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P = .002); the aHR for all-cause mortality among premenopausal women was 1.35 compared with postmenopausal women (P < .001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P < .001)

Summary

Introduction

The goal of neoadjuvant therapy is to improve surgical outcomes by inducing tumor shrinkage through effective systemic therapy; neoadjuvant therapy is useful for this because it can be initiated sooner than other therapies and treatment response can be assessed.[1]. Neoadjuvant or presurgical therapy refers to therapy administered before surgery It has been used for more than 2 decades to downstage locally advanced and unresectable primary breast cancers to make them operable.[10,11] Several studies, including the landmark National Surgical Adjuvant Breast and Bowel Project 18 trial, have demonstrated that the administration of the same chemotherapy in the neoadjuvant setting and the adjuvant setting is associated with similar outcomes.[12,13,14] NACT is conventionally used to downstage locally advanced and unresectable primary breast cancers, numerous studies have identified neoadjuvant endocrine therapy (NET) as an alternative to chemotherapy for strongly HR-positive and ERBB2-negative tumors.[15,16,17,18,19]

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