Abstract

Takuya Moriya
Department of Pathology, Tohoku University Hospital, Japan

Breast carcinomas are fundamentally heterogenous, histopathologically. Once the tumor is resected, pathologists are requested to determine many information from the tumor, to select adjuvant therapy and predict patient’s survival. They include the factors for the tumor aggressiveness, and according to the operative procedures, the extent of the tumor should be evaluated. Recently, according to the development of less invasive diagnostic procedures (ie. fine-needle aspiration cytology, core-needle biopsy), it is also necessary to evaluate their aggressiveness, preoperatively.

There are several important “prognostic factors”, which should always be included into the pathology report, and the international consensus guideline was proposed at The International Expert Consensus on the Primary Therapy of Early Breast Cancer 2005 Meeting at St. Gallen, Switzerland, in January 2005. They proposed the risk categories for operative breast carcinomas (The meeting highlight was published on “Ann Oncol. 16:1569-83, 2005”). In addition to the histological subtype, they are as follows.

• Axillary lymph node status: This is the strongest and the best prognostic factors than any others. The prognosis is significantly poor if the node metastasis exists. In addition, number of positive nodes (ie. 1-3 / 4 or more) is of value. The significance of micrometastasis ( metastatic focus 2mm or less in size ) and isolated tumor cells (less than 0.2mm) in sentinel lymph nodes is still controversial.
• Tumor size: The maximum diameter of invasive component is significant. The large tumor is generally more aggressive. The TNM classification divide primary tumor size as Tis (carcinoma in situ: DCIS and LCIS), T1(2cm or less)(subdivides as T1mic-less than 0.1mm / T1a-0.5cm or less / T1b-1cm or less / T1c), T2 (2.1-5.0cm), T3 (more than 5cm) and T4 (any size but with skin or chest wall invasion).
• Grade: Either nuclear or histological grade is important. In any classifications, they divide carcinoma into three tires (low-, intermediate- high-grade or G1/G2/G3). Of course high-grade/G3 is more aggressive. On of the famous system is modified Bloom and Richardson (Nottingham classification) by Elston and Ellis (Histopathology 19: 403-410, 1991).
• Peritumoral vascular invasion: Especially lymphovacular (lymphatic) invasion is visible on H&E glass slides. It may be associated with local recurrence after breast conserving surgery in our experience (Ishida T et al.: Jpn J Clin Oncol 33: 161-166, 2003). Immunostains for lymphatic endothelium is sometimes useful. Venous invasion may also be important to predict blood-borne distant metastasis but standard procedures had not been established yet.
• Hormone receptors: Estrogen receptor (ER) and progesterone receptor (PR) are simultaneously evaluated immunihistochemically. Around 70-80% of breast carcinomas are positive for ER/PR. It is important to predict the indication for hormonal therapy. ER-positive and node negative carcinomas are usually well differentiated and have better prognosis.
• HER2/neu: Usually immunohistochmeical evaluation for overexpressed cell surface products, according to the amplification of HER2(c-ebB-2) gene. About 20% of breast carcinomas show the overexpression. Although HER2-positive cases are more aggressive, the therapy using monoclonal antibody for HER2 had been proposed, and it may block HER2 receptor and will reduce the tumor growth.
• Histological type: The most of invasive carcinomas are invasive ductal carcinoma, not otherwise specified (IDC-NOS). However, some are special subtypes and these characters themselves may be associated with the tumor aggressiveness (grading may be more important, though).
• Others: Younger patient’s age (35yo or less) is more likely to be associated with the aggressive, if the other factors are the same.