Breast
Protocol applies to
all carcinomas of the breast.
Procedures
• Cytology
• Biopsy (incisional, core needle)
• Complete Excision less than Total Mastectomy (with or without axillary contents)
• Mastectomy (total, modified radical, radical)
I. Cytologic material back Top Main Page
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information (Note A)
a. Relevant history
b. Physical or mammographic findings
c. Procedure (e.g., fine needle aspiration)
d. Anatomic site(s) of specimen(s) (e.g., right breast, upper outer quadrant, subareolar)
e. Type(s) of specimen(s) (e.g., nipple discharge, aspirate)
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Number of slides received, if appropriate
c. Quantity and appearance of fluid specimen, if appropriate
d. Other (e.g., cytologic preparation from tissue)
e. Results of intraprocedural consultation
2. Material submitted for microscopic evaluation (e.g., smear; cytocentrifuge, touch or filter preparation; cell block)
3. Special studies (specify)
1. Adequacy of specimen (if unsatisfactory for evaluation, specify reason)
2. Tumor
a. Histologic type, if possible
b. Other features (e.g., nuclear grade, necrosis)
3. Additional pathologic findings, if present
4. Results/status of special studies (specify)
5. Comments
a. Correlation with intraprocedural consultation, as appropriate
b. Correlation with results of other specimens, as appropriate
c. Correlation with clinical information, as appropriate
II. Biopsy (incisional, core needle) back Top Main Page
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information (Note A)
a. Relevant history
b. Physical or mammographic findings
c. Clinical diagnosis, if known
d. Procedure (e.g., percutaneous core biopsy, image-guided stereotactically guided core biopsy, incisional biopsy)
e. Operative findings, as appropriate
f. Anatomic site(s) of specimen(s) (e.g., right breast, upper outer quadrant, subareolar)
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Size (three dimensions, or number and size of cores/fragments)
c. Descriptive features (e.g., color, consistency)
d. Other features (e.g., prior biopsy site)
e. Results of intraoperative consultation
2. Tissue submitted for microscopic evaluation
a. Submit entire specimen including tissue used for frozen section (unless saved for special studies)
3. Special studies (specify) (Note B)
1. Tumor
a. Histologic type(s) (Note C)
b. Histologic grade (Note D)
c. Mitotic figure count
d. Extent of any associated DCIS (Note E)
e. Microcalcifications (Note F)
f. Vascular invasion (Note G)
2. Result/status of special studies
a. Hormonal receptors
b. Other(s) (specify)
3. Additional pathologic findings, if present
4. Comments
a. Correlation with intraoperative consultation, as appropriate
b. Correlation with results of other specimens, as appropriate
c. Correlation with clinical information, as appropriate
III. Complete excision of tumor less than total mastectomy (with or without axillary contents). Includes wire-guided (localization) excision. back Top Main Page
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information (Note A)
a. Relevant history
b. Physical or mammographic findings
c. Clinical diagnosis, if known
d. Procedure (e.g., excisional biopsy, tylectomy, partial mastectomy, as specified by surgeon)
e. Operative findings, as appropriate
f. Anatomic site of specimen (e.g., right breast, upper outer quadrant, subareolar)
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Tissue(s) included
c. Received sectioned/unsectioned before receipt (Note H)
d. Size of specimen (three dimensions if removed in one piece)
e. Dimensions and description of skin, if included
f. Orientation (if specified by surgeon) and margin designation (e.g., ink) (Note I)
g. Results of intraoperative consultation
2. Tumor
a. Size (single greatest dimension) (Note J)
b. Descriptive features (e.g., degree of circumscription, consistency, mucoid appearance)
c. Correlation with imaging studies including specimen radiograph (Note F)
d. Relation to surgical margins (Note I)
3. Regional lymph nodes (if appropriate) (Note K)
a. Number identified, if possible
b. Location (if specified by surgeon)
c. Size of the largest nodal metastasis if visible
4. Additional pathologic findings (e.g., prior biopsy, prosthetic implant, fibrocystic changes), if present
5. Tissue(s) submitted for microscopic evaluation (Note L)
b. Margin(s), as appropriate (Note I)
c. Other lesion(s)
d. Lymph nodes (Note K)
e. Frozen section tissue fragment(s) (unless saved for special studies)
6. Special studies (specify) (Note B)
1. Tumor
a. Histologic type(s) (Note C)
b. Histologic grade (Note D)
c. Mitotic figure count
d. Extent of any associated DCIS, (Notes E and I)
e. Microcalcifications (Note F)
f. Verification of tumor size (Notes J and M)
g. Extent of invasion (Note M)
h. Vascular invasion (Note G)
i. Involvement of skin, if possible (Note M)
2. Status of surgical margins, as appropriate (Note I)
a. No tumor
b. DCIS at margin
c. Invasive carcinoma at margin (specify margin) (specify macroscopic or only microscopic)
3. Additional pathologic findings, if present
4. Regional lymph nodes (Note K)
a. Total number examined (specify location if indicated by surgeon)
b. Number involved by tumor (note extranodal extension, if present)
c. Size(s) of the largest nodal metastasis
5. Distant metastasis (specify site[s]) (Note M)
6. Results/status of special studies (specify) (Note B)
a. Hormonal receptors
b. Other(s) (specify)
7. Comments
a. Correlation with intraoperative consultation, as appropriate
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, as appropriate
IV. Mastectomy (total, modified radical, radical) back Top Main Page
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information (Note A)
a. Relevant history
b. Physical or mammographic findings
c. Clinical diagnosis, if known
d. Procedure (e.g., simple mastectomy, modified radical mastectomy)
e. Operative findings, as appropriate
f. Anatomic site of specimen (e.g., right breast)
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Tissue(s) included
c. Size of breast
d. Dimensions and description of skin
e. Location of biopsy site or tumor (e.g., quadrant, relation to deep margin)
f. Results of intraoperative consultation
2. Tumor
a. Size (single greatest dimension) (Note J)
b. Descriptive features (e.g., degree of circumscription, consistency, mucoid appearance)
c. Relation to surgical margins (Note I)
3. Regional lymph nodes (if appropriate) (Note L)
a. Number identified, if possible
b. Location (if specified by surgeon)
c. Size of the largest nodal metastasis if visible
4. Additional pathologic findings (e.g., prior biopsy, prosthetic implant, fibrocystic changes), if present
5. Tissues submitted for microscopic evaluation (Note L)
b. Biopsy site, needle track (if identified)
c. Margin(s), as appropriate
d. Nipple
e. Additional breast tissue (quadrants not involved by tumor)
f. Other lesions
g. Lymph nodes (Note K)
h. Frozen section tissue fragment(s) (unless saved for special studies)
6. Special studies (specify) (Note B)
1. Tumor
a. Histologic type(s) (Note C)
b. Histologic grade (Note D)
c. Mitotic figure count
d. DCIS, if present (Note E)
e. Microcalcifications (Note F)
f. Verification of tumor size (Notes J and M)
g. Extent of invasion (Note M)
h. Vascular invasion (Note G)
i. Involvement of other tissues (e.g., skin, chest wall) (Note M)
2. Regional lymph nodes, if appropriate (Note K)
a. Total number examined (specify location if indicated by surgeon)
b. Number involved by tumor (note extranodal extension of tumor, if present)
c. Size(s) of the largest nodal metastasis
3. Additional pathologic findings, if present (specify)
4. Distant metastasis (specify site[s]) (Note M)
5. Results/status of special studies (specify) (Note B)
a. Hormonal receptors
b. Other(s)
6. Comments
a. Correlation with intraoperative consultation, as appropriate
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, as appropriate
EXPLANATORY NOTES
A. Clinical Information back Top Main Page
The pathologist should have all relevant clinical information. Elements of the history that are important for breast cancer include family history, previous therapeutic irradiation to the breast, history of collagen vascular disease, nipple discharge, previous biopsy or other treatment, and especially whether the patient is currently pregnant or nursing.(1) It is important for the pathologist to know the physical and mammographic findings, such as whether the lesion was palpable or detected only by imaging studies, whether suspicious microcalcifications were seen, or whether the tumor is solid or cystic. Correlating the histologic features with the imaging studies is particularly important for image-guided core biopsies to ensure that the mammographic abnormality has been sampled and examined microscopically.
B. Special Studies back Top Main Page
Fresh tissue should not be used for special studies (e.g., hormone receptor analysis by ligand binding assay) unless the neoplasm is of sufficient size that histologic evaluation will not be compromised. When needed, hormone receptor analysis by immunohistochemistry and many other studies can be performed on routinely fixed, paraffin-embedded tissue. Besides a formal interpretation, each pathology report should specify the fixative used if other than formalin, the antibody clone and vendor, and results of control stains. Any deviation from the laboratory’s standard staining and antigen retrieval protocol should be mentioned. The percentage of positive cells should also be mentioned when clinically relevant.
C. Histologic Type back Top Main Page
This protocol applies to all carcinomas of the breast. The World Health Organization (WHO) classification of breast carcinoma is presented below, although the protocol does not preclude the use of other classifications or histologic types, such as that published in the Armed Forces Institute of Pathology Fascicle on breast tumors.(2,3)
• Noninvasive carcinoma (NOS)
- Ductal carcinoma in situ
- Lobular carcinoma in situ
• Invasive carcinoma (NOS)
-Invasive ductal
- Invasive ductal carcinoma with an extensive intraductal component
-Invasive lobular*
-Mucinous**
-Medullary***
-Papillary****
-Tubular
-Adenoid cystic
-Secretory (juvenile)
-Apocrine
-Cribriform
- Paget’s disease of the nipple
- with invasive carcinoma
- without invasive carcinoma
-Carcinoma with metaplasia
-Squamous type
- Spindle cell type
- Cartilaginous and osseous type
- Mixed type
- Inflammatory
- Other(s) (specify)
*Classic invasive lobular carcinoma, which has a better prognosis than invasive carcinoma, NOS, is diagnosed only when the tumor exhibits a single file growth pattern, a monotonous population of small cells with very low grade nuclei, and low cell density. Tumors with a diffuse infiltrative growth pattern that do not fulfill these criteria should be reported by histologic grade with the suffix “with lobular features” (or “lobular variant”). Such tumors are separately identified because this growth pattern has been associated with extensive intramammary growth and distinctive patterns of metastasis.
** The diagnosis of pure mucinous carcinoma requires the presence of low grade nuclei and extracellular mucin in at least 90% of the tumor. Tumors with less extensive mucin production should be reported by histologic grade with the suffix “with mucinous features.”
*** The diagnosis of medullary carcinoma requires strict adherence to diagnostic criteria: a sharply circumscribed tumor border, high histologic grade with patternless, syncytial sheets of large, undifferentiated tumor cells, a substantial and diffuse lymphoplasmacytic infiltrate between cellular nests, and scant fibrous stroma. Tumors lacking all of these features should be reported by histologic grade.
**** The diagnostic category of papillary carcinoma should always be qualified as to invasive or noninvasive.
D. Histologic Grade back Top Main Page
All invasive breast carcinomas with the exception of medullary carcinoma (as defined in Note E) should be graded. The grading system used must be specified in the report, and the Nottingham combined histologic grade (Elston-Ellis modification of Scarff-Bloom-Richardson grading system) is recommended.(4,5) Grading of large core needle biopsies may be done when the quantity of tissue available is sufficient. Within each stage grouping there is a relation between histologic grade and outcome.(6)
The Nottingham combined histologic grade depends on the extent of tubule formation, the extent of nuclear pleomorphism, and the mitotic count. Each variable is given a score of 1, 2 or 3, and the scores added to produce a grade. The mitotic score is determined by the number of mitotic figures found in 10 consecutive high power fields in the most mitotically active part of the tumor. Only clearly identifiable mitotic figures (e.g., cells in prophase, metaphase or anaphase) should be counted; hyperchromatic, karyorrhectic or apoptotic nuclei are excluded. Because of variations in field size, the high power field size must be determined for each microscope, and the appropriate point score determined accordingly. Using a micrometer to measure the field diameter of the microscope is recommended.
The following tabulation relates to the use of 25x objective with a field diameter of 0.59 mm and a field area of 0.274 mm2.(5)
Majority of tumor: >75% 1
Moderate: 10% to 75% 2
Minimal: <10% 3
Small regular nuclei 1
Moderate increase in size, etc. 2
Marked variation in size, nucleoli, chromatin clumping, etc. 3
Mitotic count (see
also below)
<10 mitoses per 10 HPF 1
10-20 mitoses per 10 HPF 2
>20 mitoses per 10 HPF 3
For a 40x objective with a field diameter of 0.44 mm (area = 0.152 mm2), the equivalent scoring of mitotic activity is as follows:
0-5 mitoses per 10 HPF 1
6-10 mitoses per 10 HPF 2
>10 mitoses per 10 HPF 3
The total score is then added and the grade assigned as follows.
Grade I 3 - 5 points
Grade II 6 - 7 points
Grade III 8 - 9 points
E. Ductal Carcinoma In Situ (DCIS) back Top Main Page
The following histologic features of DCIS should be included in the pathology report:(7)
1. Nuclear grade
Grade 1: Monotonous nuclei, 1.5 - 2.0 RBC diameters, with finely dispersed chromatin and only occasional nucleoli.
Grade 2: Neither nuclear grade 1 nor nuclear grade 3.
Grade 3: Markedly pleomorphic nuclei, usually >2.5 RBC diameters, with coarse chromatin and multiple nucleoli.
2. Presence or
absence of necrosis
3. Architectural
pattern(s)
Comedo
Papillary
Micropapillary
Solid
Although not required for pT classification and stage assignment, the extent (size) of DCIS is an important factor in patient management. Mammographic assessment of DCIS, usually based on distribution of calcifications, frequently underestimates the size of DCIS.(8) While precise measurement may be impossible on non-palpable, grossly inapparent lesions, the pathologist should estimate the size or extent of DCIS and include this in the report. Methods for estimating the extent of DCIS include directly measuring the lesion when confined to a single histologic slide, determining size by submitting the entire specimen in sequence and in sections of uniform thickness, and estimating the percentage of tissue involved in relation to the total specimen.(9)
In breast carcinomas with both invasive and in situ components, the pathology report should specify whether an extensive intraductal component (EIC) is present. EIC is identified when DCIS comprises a substantial portion of the main tumor mass (approximately 25%) and extends into the surrounding breast parenchyma. Cases in which the lesion is primarily DCIS with foci of invasion are also classified as EIC.(9a) This finding is associated with an increased risk of local recurrence when the surgical margins are not evaluated or focally involved.(9b) The finding appears to have less significance when DCIS does not extend close to any of the margins following careful histologic evaluation.
F. Microcalcifications back Top Main Page
If the biopsy is done for microcalcifications, their presence in the specimen must be confirmed by specimen radiography and microscopy. Ultimately, the pathologist must be satisfied that the lesion responsible for the calcifications is present in the specimen and that it has been examined microscopically. The location of the calcifications in relation to the tumor or other lesions should also be indicated.
If calcifications can be seen in the specimen radiograph but not in the initial histologic sections, deeper levels should be examined. If needed, radiographs of the paraffin block(s) may be obtained to see if calcifications remain in the block(s). If microcalcifications cannot be confirmed by routine microscopic evaluation, polarized light may be helpful, since calcium oxalate crystals are birefringent but unstained in hematoxylin-eosin sections. On rare occasions calcifications do not survive tissue processing.
G. Vascular or Lymphatic Invasion back Top Main Page
Peritumoral vascular invasion should be noted because it has been associated with local failure and reduced overall survival.(10,11) Distinguishing lymphatic channels from blood vessels is unnecessary. While sometimes difficult to identify in skin biopsies, documenting the presence of dermal lymphatic invasion is particularly important because of its strong association with inflammatory breast carcinoma.(12)
H. Specimen Examination back Top Main Page
It should be noted whether the tumor was sectioned prior to receipt, since this may preclude proper marking of the surgical margins of excision as well as ascertaining the dimensions of the specimen or tumor. Evaluation of margins does not apply to a diagnostic incisional biopsy.
I. Orientation and Identification of Surgical Margins back Top Main Page
Whenever feasible, the specimen should be oriented so the pathologist can identify specific margins. This is particularly important for excisions less than total mastectomy, where each margin (e.g., superior, inferior, medial, lateral, deep) may be important. Identification of surgical margins accomplishes two primary goals: to specifically identify margins (if any) that are involved by tumor, and to measure the distance from the tumor to specific margins. Data indicate that the most significant predictors of local control after breast conservation treatment with lumpectomy and radiation are the status of the surgical margins and the presence or absence of an extensive intraductal component (EIC).(13) Correlating mammograms with the pathologic findings and assessing surgical margins are particularly important in patients with EIC.(13a)
Orientation may be done by sutures or clips placed on the specimen surface or by other means of communication between surgeon and pathologist, and should be documented in the pathology report. Margins can be identified in several ways including the use of multiple colored inks, by submitting the margins in specific cassettes, or by the surgeon submitting each margin as a separately excised specimen. If inks are used, care should be taken to avoid penetration deep into the specimen.
Macroscopic or microscopic involvement of surgical margins by invasive carcinoma or DCIS should be noted in the report. If the specimen is oriented, the specific site(s) of involvement (e.g., superior) should also be reported. When possible, the pathologist should report the distance from the tumor to the closest margin. Blocking of tissue should be directed to evaluating the distance from the edge of the tumor to the resection margin, in addition to other sampling.
J. Tumor Size back Top Main Page
Tumor size is a powerful predictor of tumor behavior.(14) The tumor should be measured in at least two dimensions, and the single greatest dimension of the invasive component used for determining tumor stage. The size of the tumor, as measured by gross examination, must be verified by microscopic examination. If there is a discrepancy between gross and microscopic tumor measurement, the microscopic measurement of the invasive component takes precedence and should be used for tumor staging. For pT1 lesions or those with an extensive in situ component, measurement of tumor size on the histologic slide is more accurate than gross measurement. For tumors with both invasive and in situ components, only the invasive component is included in the tumor measurement for pT classification and stage assignment (see Note M below). When two or more distinct invasive tumors are present, each is separately measured and reported; they are not combined into a single larger size. Determination of tumor size may not be possible with a core or incisional biopsy.
K. Lymph Nodes back Top Main Page
Grossly uninvolved nodes should be submitted in their entirety for histologic examination, while representative sections of grossly positive nodes may be submitted. Small nodes may be submitted intact, but larger nodes should be sectioned for proper fixation and examination.
The pathology report should clearly state the total number of lymph nodes examined, the total number of involved nodes, and the greatest dimension of the largest metastatic focus. A single microscopic section from each lymph node block is considered sufficient for routine evaluation. The presence of extranodal tumor extension should be included in the pathology report since it may be is associated with a higher frequency of axillary recurrence.
A solitary focus of tumor in a single node that is visualized by routine histologic examination and measures < 0.2 cm in greatest dimension is classified as a micrometastasis. While the prognosis for patients with a solitary micrometastasis has been reported to be better than those with larger metastatic deposits, the significance of multiple micrometastases in one node or multiple lymph nodes with metastases of that size is unknown. We recommend that these be classified as pN1a. The number of nodes that contain micrometastases should be clearly specified in the pathology report since this may affect treatment.
The significance of cells found only by immunohistochemistry or molecular methods is unsettled. We recommend that these findings be reported separately from histologically-detected micrometastases and classified as pN0.
L. Specimen Sample back Top Main Page
The number of sections submitted varies with the size and character of the specimen, the nature of the underlying neoplastic process, and whether the surgical margins need to be assessed. If the biopsy is performed because of a mammographic abnormality, the entire mammographic lesion (not necessarily the entire specimen) should be submitted when practical. For excisions less than total mastectomy, blocking of tissue includes evaluating the resection margins.
M. TNM and Stage Groupings back Top Main Page
The TNM Staging System for carcinoma of the breast of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended and shown below.(15,16) Definitions for classifying the primary tumor (T) are the same for clinical and for pathologic classification. The telescoping method of classification can be applied. If the measurement is made by physical examination, the examiner will use the major headings (T1, T2, or T3). If other measurements, such as mammographic or pathologic, are used, the telescoped subsets of T1 can be used.
By AJCC/UICC convention, the designation “T” of the TNM classification refers exclusively to the first resection of a primary tumor. The prefix symbol “p” refers to the pathologic classification of the TNM (pTNM), as opposed to the clinical classification. Pathologic classification is based on gross and microscopic examination. Therefore, pT entails resection of the primary tumor or a biopsy adequate to evaluate the highest pT category; pN entails removal of axillary lymph nodes; and pM requires microscopic examination of distant lesions. Clinical classification (cTNM) is usually carried out by the clinician before treatment or when pathologic classification is not possible.
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple with no tumor*
T1 Tumor 2 cm or less in greatest dimension
T1mic Microinvasion 0.1 cm or less in greatest dimension**
T1a More than 0.1 cm but not > 0.5 in greatest dimension
T1b More than 0.5 cm but not > 1 cm in greatest dimension
T1c More than 1 cm but not > 2 cm in greatest dimension
T2 Tumor > 2 cm but not > 5 cm in greatest dimension
T3 Tumor > 5 cm in greatest dimension
T4 Tumor of any size with direct extension to chest wall or skin.
T4a Extension to chest wall
T4b Edema (including peau d’orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast
T4c Both (T4a and T4b)
T4d Inflammatory carcinoma***
* Paget’s disease associated with a tumor is classified according to the size of the tumor.
** Microinvasion is extension of cancer cells beyond the basement membrane into adjacent tissues with no focus more than 0.1 cm in greatest dimension. When there are multiple foci of microinvasion, the size of the largest focus only is used to classify the microinvasion: do not use the sum of all the individual foci. The presence of multiple foci should be noted, as with multiple larger invasive carcinomas.
*** Inflammatory carcinoma of the breast is characterized by diffuse, brawny induration of the skin with an erysipeloid edge, usually with no underlying mass. If the skin biopsy is negative and there is no localized measurable primary cancer, the T category is pTX when pathologically staging a clinical inflammatory carcinoma (T4d). Dimpling of the skin, nipple retraction or other skin changes, except those in T4b and T4d, may occur in T1, T2, or T3 without affecting the classification.
Regional Lymph Nodes
(pN)
NX Regional lymph nodes cannot be assessed (e.g., previously removed, or not removed for pathologic study)
N0 No regional lymph node metastasis
N1 Metastasis to movable ipsilateral axillary lymph node(s)
N1a Only micrometastasis (none > 0.2 cm in greatest dimension)
N1b Metastasis to lymph node(s), any > 0.2 cm in greatest dimension
N1bi Metastasis in 1 to 3 lymph nodes, any > 0.2 cm and all < 2 cm in greatest dimension
N1bii Metastasis to 4 or more lymph nodes, any > 0.2 cm and all < 2 cm in greatest dimension
N1biii Extension of tumor beyond the capsule of a lymph node, metastasis less than 2 cm in greatest dimension
N1biv Metastasis to a lymph node 2 cm or more in greatest dimension
N2 Metastasis to ipsilateral axillary lymph node(s) fixed to one another or to other structures
N3 Metastasis to ipsilateral internal mammary lymph node(s)
There are instances when the pathologist cannot make this determination because the complete staging procedure, such as a lymph node dissection, has not been performed or because information about a prior procedure is unavailable. In such situations an “X” is used rather than a number in the TNM designation.
Distant Metastasis
(M)
MX Presence of distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis (includes metastasis to ipsilateral supraclavicular lymph node(s)
Stage Groupings
Stage 0 Tis N0 M0
Stage I T1* N0 M0
Stage IIA T0 N1 M0
T1* N1** M0
T2 N0 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIA T0 N2 M0
T1* N2 M0
T2 N2 M0
T3 N1, N2 M0
Stage IIIB T4 Any N M0
Any T N3 M0
Stage IV Any T Any N M1
* T1 includes T1mic.
**The prognosis of patients with pN1a is similar to that of patients with pN0.
Tumor remaining in a patient after therapy with curative intent (e.g., surgical resection) is categorized by a system known as R classification, shown below. This classification may be used by the surgeon to indicate the known or assumed status of the completeness of the surgical resection. For the pathologist, the R classification is relevant only to the margins of surgical resection specimens; patients with tumor involving the resection margins on pathologic examination may be assumed to have residual tumor. Such patients may be classified as to whether the involvement is macroscopic or microscopic.
RX Presence of residual tumor cannot be assessed
R0 No residual tumor
R1 Microscopic residual tumor
R2 Macroscopic residual tumor.
Tumor remaining in a resection specimen following previous (neoadjuvant) treatment of any type (radiation therapy alone, chemotherapy therapy alone, or any combined modality treatment) is codified by the TNM using a prescript “y” to indicate the post-treatment status of the tumor (e.g., ypT1). The classification of residual disease may be a predictor of postoperative outcome. In addition, the ypTNM classification provides a standardized framework for the collection of data needed to accurately evaluate new neoadjuvant therapies.
Tumor that is locally recurrent after a documented disease-free interval following surgical resection is classified according to the TNM categories but modified with the prefix “r” (e.g., rpT1).
Although the pathologist provides information about the individual pTNM categories based on examination of the surgical specimen, the referring physician usually has the responsibility for grouping the TNM categories into a stage of disease.
1. Winchester DP, Cox JD, et al. Standards for diagnosis and management of invasive breast carcinoma. CA Canc J Clin. 1998; 48:83-107.
2. Rosen PP, Oberman HA. Tumors of the Mammary Gland. In: Atlas of Tumor Pathology. 3rd ed. Fascicle 7. Washington, DC: Armed Forces Institute of Pathology, American Registry of Pathology; 1993.
3. Histological Typing of Breast Tumours. 2nd ed. In: International Classification of Tumours. Geneva, Switzerland: World Health Organization; 1981.
4. Bloom HJG, Richardson WW. Histological grading and prognosis in breast carcinoma: a study of 1049 cases of which 359 have been followed for 15 years. Br J Cancer. 1957; 11:359-377.
5. Elston CW, Ellis JO. Pathological prognostic factors in breast cancer: experience from a long study with long-term follow-up. Histopathology. 1991; 19:403-410.
6. Henson DE, Ries L, Freedman LS, Carriaga M. Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. Cancer. 1991; 68:2142-2149.
7. Schwartz GF, Lagios MD, Carter D, et al. Consensus conference on the classification of ductal carcinoma in situ. Cancer. 1997; 80:1798-1802.
8. Holland R, Hendriks JHCL, Verbeek ALM, et al. Extent, distribution, and mammographic/histological correlations of breast ductal carcinoma in situ. Lancet. 1990; 335:519-522.
9. Winchester DP, Strom EA, et al. Standards for diagnosis and management of ductal carcinoma in situ (DCIS) of the breast. CA Cancer J Clin. 1998; 48:108-128.
9a. Connolly JL, Boyages J, Nixon AJ, et al. Predictors of breast recurrence after conservative surgery and radiation therapy for invasive breast cancer. Mod Pathol. 1998; 11:134-139.
9b. Gage I, Schnitt SJ, Nixon AJ, et al. Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy. Cancer. 1996; 78:1921-1928.
10. Lee A, DeLellis R, Silverman M, Heatley GJ, Wolfe H. Prognostic significance of peritumoral lymphatic and blood-vessel invasion in node-negative carcinoma of the breast. J Clin Oncol. 1990; 8:1457-1465.
11. Pinder S, Ellis IO, O’Rourke S, et al. Pathological prognostic factors in breast cancer. Vascular invasion: relationship with recurrence and survival in a large series with long-term followup. Histopathology. 1994; 24:41-47.
12. Bonnier P, Charpin C, Lejeune C, et al. Inflammatory carcinomas of the breast: a clinical, pathological, or a clinical and pathological definition. Int J Cancer. 1995; 62;382-385.
13. Smitt MC, Nowels KW, Zdeblick MJ, et al. The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer. 1995; 76:259-267.
13a. Stomper PC, Connolly JL. Mammographic features predicting an extensive intraductal component in early stage infiltrating ductal carcinoma. AJR. 1992; 158:269-272.
14. Leitner S, Swern AS, Weinberger D, Duncan LJ, Hutter RVP. Predictors of recurrence for patients with small (one centimeter or less) localized breast cancer (T1a,b N0 M). Cancer. 1995; 76:2266-2274.
15. Fleming ID, Cooper JS, Henson DE, et al., eds. AJCC Manual for Staging of Cancer. 5th ed. Philadelphia, Pa: Lippincott Raven; 1997.
16. Sobin LH, Wittekind CH, eds. International Union Against Cancer (UICC). TNM Classification of Malignant Tumours. 5th ed. New York, NY: Wiley-Liss; 1997.
BIBLIOGRAPHY
Allred DC, Harvey HM, Berardo MD, et al. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998; 11:155-168.
Association of Directors of Anatomic and Surgical Pathology. Immediate management of mamographically detected breast lesions. Hum Pathol. 1993; 24:689-690.
Baak JPA. Mitosis counting in tumors. Hum Pathol. 1990; 21:683-685.
Bellamy COC, McDonald C, Salter DM, Chetty U, Anderson TJ. Noninvasive ductal carcinoma of breast: the relevance of histologic categorization. Hum Pathol. 1993; 24:16-23.
Clark GM, Mathieu MC, Owens MA, et al. Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients. J Clin Oncol. 1992; 10:428-432.
Connolly JL, Schnitt SJ. Evaluation of breast biopsy specimens in patients considered for treatment by conservative surgery and radiation therapy for early breast cancer. Pathol Annu. 1988; 23; (pt 1):1-23.
Contesso G, Mouriesse H, Friedman S, Genin J, Sarrazin D, Rouesse J. The importance of histologic grade in long-term prognosis of breast cancer; A study of 1,010 patients uniformly treated at the Institute Gustave-Roussy. J Clin Oncol. 1987;5:1378-1386.
Fisher ER, Gregorio RM, Fisher B, Redmond C, Vellios F, Sommers SC. The pathology of invasive breast cancer: A syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol No. 4). Cancer. 1975; 36:1-78.
Lagios MD, Westdahl PR, Margolin FR, Roses MR. Duct carcinoma in situ; Relationship of extent of noninvasive disease to the frequency of occult invasion, multicentricity, lymph node metastases, and short-term treatment failures. Cancer. 1982; 50:1309-1314.
Lennington WJ, Jensen RA, Dalton LW, Page DL. Ductal carcinoma in situ of breast: Heterogeneity of individual lesions. Cancer. 1994; 73:118-124.
Miller WR. Prognostic factors in breast cancer. Br J Cancer. 1992; 66:775-776.
Page DL, Jensen RA, Simpson JF. Routinely available indicators of prognosis in breast cancer. Br Cancer Res Treat. 1998;51:195-208.
Page DL. Prognosis and breast cancer: Recognition of lethal and favorable prognostic types. Am J Surg Pathol. 1991;15:334-349.
Page DL, Anderson TJ, Sakamoto G. Infiltrating carcinoma: major histological types. In: Page DL, Anderson TJ eds. Diagnostic Histology of the Breast. New York, NY: Churchill Livingstone; 1987:193-235.
Rosen PP, Groshen S. Factors influencing survival and prognosis in early stage breast carcinoma (T1N0M0-T1N1M0): assessment of 644 patients with median follow-up of 18 years. Surg Clin N Am. 1990;70:937-962.
Schnitt SJ, Conolly JL. Processing and evaluation of breast excision specimens: a clinically oriented approach. Am J Clin Pathol. 1992;98:125-137.
Schnitt SJ, Wang HH. Histologic sampling of grossly benign breast biopsies. how much is enough? Am J Surg Pathol. 1989;13:505-512.
Silvestrini R. Proliferation markers in breast cancer. Eur J Cancer. 1993;29A:1501-1502.
Veronese SM, Gambacorta M, Gottardi O, Scanzi F, Ferrari M, Lampertico P. Proliferation index as a prognostic marker in breast cancer. Cancer. 1993;71:3926-3931.
Authors:
Patrick L. Fitzgibbons, MD; James L. Connolly, MD; David L. Page, MD
Originally published in the Archives of Pathology & Laboratory Medicine, January 1997.
Previous contributing authors:
Donald E. Henson, MD; Harold A. Oberman, MD; Robert V.P. Hutter, MD
Contributors: back Top Main Page
CAP Cancer Committee; Ronald S. Berardi, MD; William Donegan, MD; Edwin R. Fisher, MD; Barbara Fowble, MD; Melvin Greenblatt, MD; Fred Gorstein, MD; William H. Hartmann, MD (Advisor); James Ingle, MD; Robert McLelland, MD; David Page, MD; Jeanne Petrek, MD; Stuart Schnitt, MD; J. Daniel Wilkes, MD; David Winchester, MD