Staging of Breast Cancer

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Chennai Breast Centre, Chennai, India

The extent or stage of cancer at diagnosis is vital to assess the prognosis and determine the appropriate treatment. Uniform classification of cancer cases provides a method to convey clinical experiences clearly without any ambiguity. In this manner, the outcomes and efficacy of specific treatments can be assessed better.

Staging of breast cancer began with Manchester Staging in 1940, a clinical four-stage system based on local extent and distant spread. Columbia staging system was in use for a while until it was replaced by widely followed TNM classification, introduced by UICC (International Union against Cancer). AJCC developed a series of site-specific staging systems in the late 1960s. The two bodies agreed on a single staging system in the late 1980s which is currently in use. AJCC makes revisions every 6–8 years and the most recent is seventh edition published in 2010.

Translational research has led to (a) remarkable progress in molecular pathogenesis of breast cancer, (b) increasing number of prognostic factors, and (c) development of predictive factors in assessing the individual’s response to specific therapy. This has transformed cancer treatment from group-specific therapy to highly individualized therapy. AJCC keeping abreast of these developments has incorporated many nonanatomic details into staging systems. In many others, it has made it imperative to collect these nonanatomic details and mention it alongside the designated TNM stage. AJCC has consciously taken into consideration the issue of reproducibility, as a large number of patients are treated in centers devoid of cutting-edge technologies to diagnose genetic profile of a tumor and also cost is a deterrent. Thus, only details vital to treatment decisions and prognosis are included in staging.

TNM (tumor size, presence or absence of disease in regional lymph nodes, and distant metastasis) staging is done at two points, first the clinical staging based on physical examination and imaging modality and the second pathologic staging based on pathologic information obtained after surgery. Pathologic stage is generally considered accurate but clinical staging provides the basis for initial treatment decisions (surgery vs. neoadjuvant chemotherapy or palliative therapy). Pathological staging is considered more accurate than clinical staging owing to the innate limitations of clinical and imaging modalities in determining the precise tumor size and extent of locoregional spread. Nevertheless, clinical staging forms the basis for decision making in initial treatment modality. Prefix ‘c’ and ‘p’ is added for clinical staging and pathologic staging, respectively. Patients having systemic therapy (neoadjuvant chemo/radiotherapy) would have their tumors staged at the end of therapy to assess the response and direct the subsequent management (extent of surgery and adjuvant therapy). Prefix yc or yp is added for post-treatment clinical and pathologic staging.

T-Stage

The first component in staging is size of primary tumor. The T-stage is based on maximum diameter of the primary tumor. Clinical tumor size (cT) is ascertained by combination of measurements obtained in physical findings and imaging (mammogram/ultrasound/MRI) and is based on findings that are judged to be accurate for a particular case. Imaging might over or underestimate tumor size due to frequent coexistence of invasive and noninvasive components, which at present these techniques are unable to discern with certainty.

The size of the primary tumor from the resected specimen is measured for pathologic T classification before any tissue is removed for special purposes, such as prognostic biomarkers or tumor banking. For small invasive tumors that can be submitted in one section/paraffin block, the microscopic measurement is the most accurate way to determine pT. If an invasive tumor is too large to be submitted for microscopic evaluation in one tissue section/block, the gross measurement is the preferred method of determining pT. Whichever method is used, pT should be recorded to the nearest millimeter. Pathologic tumor size (pT) should be based on measuring the invasive component and not in situ component, thus a 3 cm DCIS with 8 mm invasive component is staged as T1b based on invasive component.

Special Situations

In situ classification (Tis): Pure noninvasive carcinoma or carcinoma in situ is classified as Tis with additional subclassification in parentheses. Three subtypes are defined, namely, DCIS, LCIS, and Paget’s disease without underlying mass.

Terms like intraductal carcinoma, ductal intraepithelial neoplasia are uncommonly used and are best avoided.

Paget’s disease when associated with underlying invasive carcinoma or in situ carcinoma T status should be staged based on the size of underlying component documenting the presence of Paget’s. When not associated with identifiable underlying invasive or noninvasive disease, lesions should be classified as Tis (Paget’s).

Microinvasive Carcinoma. Microinvasive carcinoma is defined as an invasive carcinoma with no focus measuring >1 mm. Microinvasive carcinomas are almost always encountered in setting of DCIS where foci of tumor invade through the basement membrane. It is less frequently associated with LCIS or absence of in situ component. Note should be made whether the invasion occurs at one place or multiple places. In cases with multiple foci, the number of foci and range of sizes of invasion should be quantified separately and not as sum of sizes. Microinvasive carcinoma has an excellent prognosis.

Multicentric Carcinomas. When more than one tumor is present in the same breast, the T-stage is based on largest of two lesions and not the sum of diameters. Multifocality should be documented.

Simultaneous Bilateral Primary Carcinomas. Each cancer is staged separately mentioning the side.

Inflammatory Carcinoma. Inflammatory carcinoma is a distinct clinical-pathologic entity characterized by diffuse erythema and edema (peau d’orange) involving a third or more of the skin of the breast which is classified as T4d. Inflammatory carcinoma is primarily a clinical diagnosis.

An underlying mass may be detected through examination (rare) or imaging (frequently). However, a tissue diagnosis is still necessary to demonstrate an invasive carcinoma in the underlying breast parenchyma or at least in the dermal lymphatics, as well as to determine biologic markers, such as estrogen receptor, progesterone receptor, and HER2 status.

Regional Lymph Nodes (N)

Regional lymph nodes include axillary nodes, ipsilateral intramammary nodes, internal mammary nodes, and supraclavicular nodes. Intramammary nodes reside within the breast tissue and are coded as axillary lymph nodes for staging purposes. Supraclavicular lymph nodes are classified as regional lymph nodes for staging purposes. Metastases to any other lymph node, including cervical, or contralateral axillary lymph nodes are classified as distant (M1).

Nodal status is assessed clinically (cN) and also pathologically (pN). N Staging in TNM has undergone major changes in recent editions. This is secondary to changes in surgical approach to axilla and understanding of tumor biology. Sentinel node has replaced axillary dissection and more small foci of metastasis in nodes are being identified that would have been missed previously. Detailed evaluation of nodes is now possible due to fewer numbers of nodes submitted for pathologic examination.

Clinical staging of nodal status was historically based on proper physical examination of axilla and supraclavicular area. However, in recent times, imaging in the form of axillary ultrasound is being used increasingly and should be considered in any patient with invasive breast cancer. Ultrasound-guided FNA can spare patients from undergoing sentinel node biopsy unnecessarily as well as saving cost and time.

Pathologic stage has become more complicated with introduction of sentinel node biopsy. A case in which the classification is based only on sentinel lymph node biopsy is given the additional designation (sn) for “sentinel node” – for example, pN1 (sn). The (sn) modifier indicates that nodal classification is based on less than an axillary dissection. When six or more nodes are found in gross examination of specimen, the modifier sn is removed. With only one to three nodes for examination, pathologists have more time to analyze multiple sections and identify metastasis.

The use of immunohistochemical and molecular methods (RT PCR) to identify node mets is being used now but clinical significance is uncertain. They are still treated as N0 but designated as N0 (i+) (IHC detected) or N0 (mol+).

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