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Borstkanker - TNM 8 (AJCC)

Onderbouwing

Bron: Giuliano A.E. MD et al: Breast Cancer—Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual (link naar originele publicatie)

 

The TNM (primary tumor [T], regional lymph nodes [N], distant metastases [M]) staging system began in 1959 as a product of the American Joint Committee for Cancer (AJCC) staging end results reporting. Changes for the eighth edition were based on evidence available from peer-reviewed literature and on findings from large, as yet unpublished databases and were carefully reviewed by a panel of breast cancer experts and AJCC representatives.

The expert panel that formulated the prior (seventh) edition of the staging manual carefully considered the introduction of biomarkers to identify groups with different molecular characteristics and different prognoses. That panel decided that evidence in the literature then available could not support the addition of biomarkers to the TNM staging classification. For the eighth edition, the expert panel concluded that the ensuing advances in clinical and laboratory science and translational research seriously challenged the relevance of the purely anatomic TNM staging for breast cancer. A better understanding of biologic markers, such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and their respective impact on prognosis, selection of therapy, and response to therapy warranted modification of the TNM staging system for breast cancer.

The panel acknowledged that the clinical utility of biologic factors such as grade, hormone receptor expression, HER2 overexpression and/or amplification, and genomic panels has become at least as important as the anatomic extent of disease to predict survival. These factors enable accurate determination of prognosis and selection of systemic therapy and increasingly are affecting locoregional management. The widespread use of immunohistochemical evaluation of these markers to permit reproducible identification of their presence in tumors has greatly altered breast cancer therapy. Although a careful review of the literature did not always result in level I evidence to support the impact of these biologic factors on prognosis, the expert panel felt that, despite the limitations of available evidence, it was essential to incorporate these factors into the revision of the AJCC staging system to remain relevant to contemporary practice.

The panel also recognized that much of the world does not have access to reliable analysis of these factors. The anatomic basis of the TNM staging classification is relevant worldwide, but staging based solely on anatomic factors remains especially relevant where biological markers are not routinely available. In addition, continuing the use of anatomic TNM staging provides continuity with the past and enables breast cancer investigators to compare groups of patients who were treated during different times over the last one-half century. TNM staging also permits current investigators to communicate with each other around the world using a standardized language that reflects tumor burden.

To ensure that the cancer care community has the necessary infrastructure in place for documenting eighth edition stage, the AJCC Executive Committee—in dialogue with the National Cancer Institute-Surveillance, Epidemiology, and End Results program; the Centers for Disease Control and Prevention; the College of American Pathologists; the National Comprehensive Cancer Network (NCCN); the National Cancer Data Base; and the Commission on Cancer - made the decision to delay implementation of the eighth edition cancer staging system to January 1, 2018. Clinicians will continue to use the latest information for patient care, including scientific content of the eighth edition manual. All newly diagnosed cases through December 31, 2017 should be staged with the seventh edition. The time extension will allow all partners to develop and update protocols and guidelines and for software vendors to develop, test, and deploy their products in time for the data collection and implementation of the eighth edition in 2018.

Innovations and Changes to Traditional Anatomic TNM

The anatomic TNM system for reporting extent of disease continues to provide quantitative classification categories for the primary tumor (T), regional lymph nodes (N), and distant metastases (M), which are combined to determine an overall stage group. Historically, the TNM anatomic stage groups have been associated with outcome measures, including overall survival (OS) and disease-free survival. When applied to groups of patients, TNM staging provides an accurate prediction of outcome. However, outcome predictions derived from groups of patients within stage groups and subgroups are more problematic when applied to individual patients who have different biologic subtypes of cancers that express different biomarkers. Thus, while anatomic TNM classifications remain the basis for the eighth edition stage groups, tumor grade, hormone receptor status, and HER2 status are important additional determinants of outcome and are now incorporated into parallel prognostic stage groups that recognize intrinsic tumor biology. Despite the predictive power of intrinsic breast cancer phenotypes, such as luminal, basal, and HER2, extent of disease also offers predictive synergy. The anatomic TNM classification provides a common language for communicating disease burden. Over time, the definitions for classification have required modification, particularly to accommodate additional subclasses of earlier stage breast cancers that are diagnosed with increasing frequency among women who undergo mammographic screening. The eighth edition of the staging manual has continued this evolution and further refined and clarified the definitions for T, N, and M. Table 1 summarizes the significant changes to the TNM classification.

 

Table 1. Summary of Changes in the Eighth Edition

CHANGE

DETAILS OF CHANGE

LEVEL OF EVIDENCE

  1. Abbreviations: AJCC, American Joint Committee on Cancer; PAM50, prediction analysis of microarray 50.

AJCC anatomic and prognostic stage groups

There are 2 stage group tables presented in this chapter:

II

 

1. The anatomic stage group table is based solely on anatomic extent of cancer as defined by the T, N, and M categories.

 

 

2. The prognostic stage group table is based on populations of persons with breast cancer that have been offered—and mostly treated with—appropriate endocrine and/or systemic chemotherapy, which includes anatomic T, N, and M plus tumor grade and the status of the biomarkers human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR).

 

Selecting the appropriate stage group table

The prognostic stage group table is preferred for patient care and is to be used for reporting of all cancer patients in the United States.

 

 

The anatomic stage group table is provided so that stage can be assigned in regions of the world where the biomarkers cannot be routinely obtained.

N/A

Definition of primary tumor (T)

Lobular carcinoma in situ (LCIS) is removed as a pathologic tumor in situ (pTis) category for T categorization. LCIS is a benign entity and is removed from TNM staging.

I

Definition of primary tumor (T)

The general rules for rounding to the nearest millimeter do not apply for tumors between 1.0 and 1.5 mm, so that these cancers are not classified as microinvasive (T1mi) carcinomas (defined as invasive tumor foci 1.0 mm or smaller). Tumors >1 mm and < 2 mm should be reported rounding to 2 mm.

II

Definition of primary tumor (T)

It is confirmed that the maximum invasive tumor size (T) is a reasonable estimate of tumor volume. Small, microscopic satellite foci of tumor around the primary tumor do not appreciably alter tumor volume and are not added to the maximum tumor size.

I

Definition of primary tumor (T)

The T categorization of multiple synchronous tumors is clarified. These are identified clinically and/or by macroscopic pathologic examination, and their presence documented using the (m) modifier for the T category. This new edition specifically continues using only the maximum dimension of the largest tumor for clinical (cT) and pathological (pT) T classification; the size of multiple tumors is not added.

I

Definition of primary tumor (T)

A clear definition is added that satellite tumor nodules in the skin must be separate from the primary tumor and macroscopically identified to categorize as T4b. Skin and dermal tumor satellite nodules identified only on microscopic examination and in the absence of epidermal ulceration or skin edema (clinical peau d’orange) do not qualify as T4b. Such tumors should be categorized based on tumor size.

I

Definition of regional lymph node (N)

The criteria for pathological measurement of lymph node metastases are clearly defined. The dimension of the area containing several or multiple tumor deposits is NOT used to determine pathological N (pN) category. The largest contiguous tumor deposit is used for pN; adjacent satellite tumor deposits are not added.

I

Definition of regional lymph node (N)

The expert panel affirmed that cNX is not a valid category unless the lymph node basin has been removed and cannot be examined by imaging or clinical examination; a cN0 category is to be assigned when any evaluation of the lymph nodes is possible and the physical examination or imaging examination is negative.

I

Definition of distant metastasis (M)

The expert panel affirmed that pM0 is not a valid category. All cases should be categorized as either cM0 or cM1; however, if cM1 is subsequently microscopically confirmed, pM1 is used (see Chapter 1 as well)

I

Postneoadjuvant therapy classification (ypTNM)

The expert panel clarified that the postneoadjuvant therapy pathological T category (ypT) is based on the largest focus of residual tumor, if present. Treatment-related fibrosis adjacent to residual invasive carcinoma is not included in the ypT maximum dimension. When multiple foci of residual tumor are present, the (m) modifier is included. The pathology report should include a description of the extent of residual tumor explaining the basis for the ypT categorization and, when possible, also should document the pretreatment cT category.

I

Postneoadjuvant therapy classification (ypTNM)

The expert panel clarified that the largest focus of residual tumor in the lymph nodes, if present, is used for ypN categorization. Treatment-related fibrosis adjacent to residual lymph node tumor deposits is not included in the ypN dimension and classification.

I

Complete pathological response

The expert panel affirmed that any residual invasive carcinoma detected by pathological examination in the breast or lymph nodes precludes posttreatment classification as a complete pathological response (pCR). If a cancer is categorized M1 (clinical or pathological) prior to therapy, the cancer is categorized as M1 after neoadjuvant therapy, regardless of the observed response to therapy.

I

Collection of biomarkers (hormone receptor assays and HER2 assay)

The expert panel determined that all invasive carcinomas should have ER, PR, and HER2 status determined by appropriate assays whenever possible.

I

Inclusion of multigene panels (when available) as stage modifiers—21-gene recurrence score (Oncotype Dx)

For patients with hormone receptor-positive, HER2-negative, and lymph node-negative tumors, a 21-gene (Oncotype Dx) recurrence score less than 11, regardless of T size, places the tumor into the same prognostic category as T1a-T1b N0 M0, and the tumor is staged using the AJCC prognostic stage group table as stage I.

I

Inclusion of multigene panels (when available) as stage modifiers—Mammaprint

For patients with hormone receptor-positive, HER2-negative, and lymph node-negative tumors, a Mammaprint low-risk score, regardless of T size, places the tumor into the same prognostic category as T1a-T1b N0 M0.

II

Inclusion of multigene panels (when available) as stage modifiers—EndoPredict

For patients with hormone receptor-positive, HER2-negative, and lymph node-negative tumors, a 12-gene (EndoPredict) low-risk score, regardless of T size, places the tumor into the same prognostic category as T1a-T1b N0 M0.

II

Inclusion of multigene panels (when available) as stage modifiers—PAM50 (Prosigna)

For patients with hormone receptor-positive, HER2-negative, and lymph node-negative tumors, a PAM50 risk–of-recurrence score in the low range, regardless of T size, places the tumor into the same prognostic category as T1a-T1b N0 M0.

II

Inclusion of multigene panels (when available) as stage modifiers—Breast Cancer Index

For patients with hormone receptor-positive, HER2-negative, and lymph node-negative tumors, a Breast Cancer Index in the low-risk range, regardless of T size, places the tumor into the same prognostic category as T1a-T1b N0 M0.

II


Lobular carcinoma in situ (LCIS) has been removed from the staging classification system and is no longer included in the pathologic tumor in situ (pTis) category. LCIS is treated as a benign entity with an associated risk for developing carcinoma in the future but not as a malignancy capable of metastases. There is a small subset of LCIS that has high-grade nuclear features and may exhibit central necrosis. This subset has been referred to as pleomorphic LCIS and has histologic features that partially overlap the features of ductal carcinoma in situ (DCIS), including the potential to develop calcifications detectable by mammography. The expert panel debated whether to include this variant of LCIS in the pTis category; however, there are insufficient data in the literature regarding outcomes and reproducible diagnostic criteria for this LCIS variant. Cases exhibiting DCIS and LCIS are classified as pTis (DCIS). The only other Tis category, pTis (Paget), is for pure Paget disease without any underlying DCIS or invasive carcinoma.


The seventh edition staging manual included rules for rounding tumor size to the nearest millimeter. This was problematic for microinvasive carcinoma of the breast. The eighth edition manual explicitly defines microinvasive pathologic T1 tumors (pT1mi) as those measuring ≤ 1.0 mm and clarifies that tumors between 1.0 and 1.5 mm should be rounded up to 2.0 mm (pT1a). Table 2 lists the primary tumor size (T) classifications.

 

Table 2. American Joint Committee on Cancer Definition of Primary Tumor (T)—Clinical (cT) and Pathological (pT)

T CATEGORY

T CRITERIA

Lobular carcinoma in situ is a benign entity and is removed from TNM staging in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, eighth edition.

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

Tis (DCIS) 

Ductal carcinoma in situ (DCIS)

Tis (Paget)

Paget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted.

T1

Tumor ≤ 20 mm in greatest dimension

T1mi

Tumor ≤ 1 mm in greatest dimension

T1a

Tumor > 1 mm but ≤ 5 mm in greatest dimension (round any measurement from >1.0-1.9 mm to 2 mm)

T1b

Tumor > 5 mm but ≤ 10 mm in greatest dimension

T1c

Tumor > 10 mm but ≤ 20 mm in greatest dimension

T2

Tumor > 20 mm but ≤ 50 mm in greatest dimension

T3

Tumor > 50 mm in greatest dimension

T4

Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4

T4a

Extension to the chest wall; invasion or adherence to pectoralis muscle in the absence of invasion of chest wall structures does not qualify as T4

T4b

Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema (including peau d’orange) of the skin that does not meet the criteria for inflammatory carcinoma

T4c

Both T4a and T4b are present

T4d

Inflammatory carcinoma (see “Rules for Classification”)

Autorisatiedatum en geldigheid

Laatst beoordeeld  :

Laatst geautoriseerd  : 07-02-2020

Initiatief en autorisatie

Initiatief:
  • Nationaal Borstkanker Overleg Nederland
  • Nederlandse Internisten Vereniging

Methode ontwikkeling

Evidence based

Volgende:
TNM 8