Preoperative Therapy in Breast Cancer: Lessons from the Treatment of Locally Advanced Disease

Abstract

The greater use of screening has changed the stage distribution of breast cancer, and an increasing number of patients are diagnosed with earlier stages of the disease. Still, locally advanced breast cancer (LABC) remains a major clinical problem in the United States and a common presentation in many parts of the world. There is no standard definition of LABC. One commonly used includes patients with large primary tumors greater than 5 cm (T3) or with skin/chest wall involvement (T4), and/or fixed axillary (N2) or ipsilateral internal mammary (N3) lymph node involvement. According to the tumor node metastasis staging, these usually include stage IIIa (T0-2N2 or T3N1-2) and stage IIIb (T4Nx or TxN3) disease. Inflammatory breast cancer (T4d) is included in most classifications despite its distinct clinical behavior and worse prognosis overall, but it serves as an example of combined modality intervention. Historically, the term LABC has been applied to those clinical presentations where the disease is considered inoperable. However, these therapeutic principles (including preoperative or primary systemic therapy [PST]) are increasingly being applied to patients presenting with tumors greater than 5 cm and negative lymph nodes (stage IIb-T3N0) or even smaller tumors, who are considered to have operable disease and a better outcome than those traditionally classified as having LABC. PST is increasingly being used in otherwise operable stage I and II patients aiming at greater rates of breast conservation and earlier efficacy assessment. This article reviews many of these issues and ongoing research questions. The Oncologist 2002;7:239-245 The Oncologist 2002;7:239-245 www.TheOncologist.comCorrespondence: Antonio C. Wolff, M.D., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Building, Room 189, 1650 Orleans Street, Baltimore, Maryland 21231-1000 Fax: 410-955-0125; e-mail: awolff@jhmi.edu Received December 21, 2001; accepted for publication February 4, 2002. ©AlphaMed Press 1083-7159/2002 The Oncologist ® Mayo Clinic Hematology/Oncology Reviews LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Better understand the current state of the art of managing patients with locally advanced breast cancer.2. Understand how primary, preoperative systemic treatment might be incorporated into the management of patients with early stage breast cancer.3. Understand the status of ongoing and recently completed clinical trials in this important area of multi-modality patient care.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME

Immediate Gene Expression Changes After the First Course of Neoadjuvant Chemotherapy in Patients with Primary Breast Cancer Disease

“…As an alternative therapeutic concept, neoadjuvant or primary systemic therapy (PST) can be offered either to those patients with larger inoperable breast cancers or to patients interested in breast-conserving surgery (45)(46)(47)(48)(49)(50)(51)(52)(53). The PST in general do not offer a survival advantage over standard adjuvant treatment, but may identify patients with a pathologically confirmed complete response (45,46).…”

The relevance of circulating epithelial tumor cells (CETC) for therapy monitoring during neoadjuvant (primary systemic) chemotherapy in breast cancer

“…In addition to tumor-size reduction aiming to achieve higher rates of breast conservation [4], this therapy may also provide information about the responsiveness of the individual tumor to chemotherapy for later application in case of relapse [5]. Different chemotherapeutic agents have shown reactivity the metastatic situation and an improvement in relapse-free survival in the adjuvant situation.…”

Role of Radiation Therapy on the Use of Primary (“Neoadjuvant”) Systemic Treatment of Breast Cancer

“…Sequentielle Chemoradiotherapieregime haben beim LABC hohe Ansprechraten erbracht. Dementsprechend stellt die Integration einer Radiotherapie im Anschluss an eine PST den heutigen Behandlungsstandard für LABC dar [27,42,44,54,70] …”