1. Introduction

Breast cancer is the most common cancer accounting for 25.1% of all cancers in women according to GLOBOCAN and the second most common cancer overall worldwide [1]. Over 1.5 million women are diagnosed with breast cancer every year, and half million women die due to breast cancer in the world each year. Although it is the fifth most common cause of

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

death from cancer in women, during last 3 decades, deaths due to breast cancer have decreased by one-third or more. It is due in part to increased screening, as well as more effective loco-regional and systemic treatment options have been established over last decades.

2.1. Genomic tools: oncotype Dx

Oncotype DX contains five reference genes (ACTB, GAPDH, GUS, RPLPO and TFRC) and 16 cancer-related genes. RNA is extracted from formalin-fixed paraffin-embedded tumor tissue, using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). The recurrence score (RS) is the result of a mathematical formula of the weighted expression of each gene, ranging from 0 to 100. The cutoff points are divided into three categories: low risk (RS < 18), intermediate risk (RS 18–30), and high risk (RS > 31). The RS has been proved to be a predictor of 10-year distant recurrence for early breast cancer through NSABP B-14 in multivariate analyses including age, tumor size, tumor grade, ER status and HER2 status [4]. Furthermore, patients with low or intermediate RS had large improvements in disease-free survival (DFS) if treated with tamoxifen (TAM), which indicated that RS was helpful in evaluating treatment response to endocrine therapy in early breast cancer. Habel et al. [5] conducted a case–control study among women with ER+, node-negative breast cancer treated with TAM and compared these with untreated patients. The RS was associated with the risk of breast cancer death in both groups (P = 0.003 and P = 0.03). Thus, the RS was strongly related to long-term mortality of breast cancer

Adjuvant Systemic Treatment in Hormone Receptor Positive, HER2 Negative Breast Cancer

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Paik et al. not only evaluated the relationship between the RS and clinical result of ER+, nodenegative early breast cancer but also explored the prognostic ability in late recurrence of breast cancer [4]. The 10-year distant recurrence rate was 6.8% in low-risk group, 14.3% in intermediate-risk group and 30.5% in high-risk group. The RS was shown to be related to distant relapse in patients who did not receive adjuvant chemotherapy, regardless of age and

RS can predict chemotherapy sensitivity in patients with ER+, node-negative breast cancer [6]. Paik et al. studied 651 cases of breast cancer who were enrolled in NSABP B-20 and randomly assigned them into a TAM group and a TAM combined with the chemotherapy group [chemotherapy regimen for cyclophosphamide & methotrexate & fluorouracil (CMF) or MF regimen, TAM + CMF/MF group] [4]. The 10-year follow-up results showed that patients with high RS had benefited from cytotoxic chemotherapy, with the 10-year metastasis rate being decreased by 27.6%. In contrast, the 10-year distant metastasis rate was decreased by an average of 1.1% in patients with low RS who received adjuvant chemotherapy. Therefore, patients with ER+ early breast cancer and high RS should benefit from chemotherapy, while patients with low RS cannot. RS can help select patients who experience little benefit of

In a phase III trial, the Trial Assigning Individualized Options for Treatment (TAILORx), there was a prospective phase to further validate the function of RS in patients with HR+, HER2 negative, node-negative breast cancer. The results from TAILORx indicated that patients with very low RS results (<11) had excellent clinical outcome with a rate of 5-year freedom from distant recurrence with endocrine therapy at 99.3% and a rate of overall survival (OS) of 98.0%, even without chemotherapy [7]. As for its excellent utility in identifying patients with good outcome, Oncotype DX RS became the only gene-expression assay that was recommended at level I evidence in the AJCC Prognostic Stage Group. In patients with HR+, node-negative

breast cancer, the RS showed excellent clinical utility to predict clinical outcomes.

among ER+ breast cancer patients treated with endocrine therapy.

tumor size and performed better than both of them (P < 0.001).

chemotherapy and can avoid the toxic effects of chemotherapy.

The risk of relapse varies substantially on the basis of individual disease. Thus, accurate estimates regarding recurrence and survival are critical for selecting patients with breast cancer who will benefit from adjuvant therapy. Decisions about the type of treatment have traditionally been based on the histopathologic parameters including lymph node status, tumor size, histologic grade, histologic subtype, patient age, and estrogen receptor (ER)/progesterone receptor (PR) status. However, these characteristics fail to characterize the biologic heterogeneity of tumors, which has important implications for treatment benefit. The advent of microarray gene expression profiles as well as sequencing of the whole genome has brought several multigene platforms into clinical use. Many of these platforms incorporate traditional markers (e.g., ER, PR, and HER2) as well as additional cancer-associated genes. Approximately 75–80% of all breast cancers are luminal A or luminal B subtypes which are hormonedependent based on the presence of ER and/or PR on tumor cells [2].

Here, the genetic and online tools which guide the adjuvant systemic treatment, options of endocrine therapy and systemic cytotoxic chemotherapy in patients with early stage HR+, HER2 -negative breast cancer will be discussed.
