Prediction of Benefit From Adjuvant Treatment in Patients With Breast Cancer

Abstract

With the increasingly early diagnosis of breast cancer and the advent of breast tumor subtyping, the need for determining which patients need adjuvant therapy has become more pressing and more complex. While clinical and pathologic features to predict benefit are valuable, the use of molecular techniques to better determine which tumors will benefit from chemotherapy is expected to further improve outcomes, reduce long-term complications, and provide cost-effective care. We will review the primary tools in clinical use: Adjuvant!, Oncotype DX®, and MammaPrint® as well as intrinsic subtypes and the plans for their further assessment in the clinical trial setting. The expected benefit from these models are that treatment recommendations for women with early-stage breast cancer will become more individualized and thereby appropriate by combining standard clinicopathologic and molecular features. This concept is currently being evaluated in multiple well-designed clinical trials.

Introduction

Breast cancer is increasingly diagnosed at earlier stages and is a disease with multiple subtypes, with differing prognostic and therapeutic implications. These two factors drive the need for determining appropriate therapy for patient subsets to avoid both undertreatment and overtreatment. Treatment guidelines based on clinical features partition women into low and high risk for recurrence1, 2 and recommend adjuvant chemotherapy for the majority of women. As per NCI guidelines, women with early-stage hormone receptor positive breast cancer and tumors > 1 cm have been recommended for chemotherapy¹ while St. Gallen's criteria suggest chemotherapy for women with tumors > 2 cm.³ Eight-year follow-up from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-20 show that for estrogen receptor (ER)–positive, lymph node–negative tumors, the addition of first-generation chemotherapy regimens (cyclophosphamide, methotrexate, and fluorouracil [CMF] or methotrexate and fluorouracil) to tamoxifen provided a 7% absolute benefit in disease-free survival (DFS; P = .001).⁴ A subset analysis of tumors ≤ 1 cm in size showed an absolute benefit of 2% in relapse-free survival (RFS; P = .7). Additionally, women aged > 50 years did benefit as much as younger women. These findings indicate that many women are overtreated and do not benefit from chemotherapy. For breast cancer researchers, a primary concern is to identify patients for whom chemotherapy is not necessary.⁵ Fortunately, there have been significant developments in the field that provide the clinician and patient with a better understanding of the benefits of adjuvant therapy and guidelines are now incorporating these tools.⁶ Herein, we review the clinical tools that are commonly used as well as those under development and the clinical trials in which they are being further evaluated.