The breasts are paired, hemispherical-shaped, glandular organs of variable size on the chest of a woman (between the 2nd and 6th ribs and anterior to pectoral muscles). They are mostly made up of adipose (fatty) tissue and connective (fibrous) tissue that surrounds and support about 12 to 20 lobes. The nipple is surrounded by the dark skin called the areola.
Epithelial breast carcinoma or adenocarcinoma (affecting epithelial cells of the glandular tissue within breast) is the most commonly encountered (more than 95% of all cases) type of breast cancer. Breast adenocarcinoma includes ductal carcinoma in situ, invasive ductal carcinoma, and invasive lobular carcinoma.
Breast Cancer Hormone Receptors: Normal breast cells and some breast cancer cells have specialized proteins on/in their surface called hormone receptors. Hormones – estrogen and progesterone can bind to these receptors (estrogen receptor [ER] and progesterone receptor [PR], respectively) and promote the growth of these cells.
Some breast cancer cells have another growth-promoting protein on/in their surface known as the human epidermal growth factor receptor 2 (HER2/neu or HER2). Certain breast cancer cells do not have any of the above receptors, that is, negative for ER, PR, and HER2. These are called triple-negative breast cancer.
TNM Staging of Breast Cancer – Clinical
Clinical TNM Staging for breast cancer is done by physical examination of the patient and loboratory and radiology investigations (discussed below).
It is called as T1 when the tumor size is less than or equal to 2 cm. T2 when the tumor is 2 cm to 5 cm. And T3 when the tumor is more than 5 cm. To understand T4 disease, first we have to know the structures. Deep to the breast there is pectoralls fascia and pectoralls major muscle.
And here lies the pectoralis minor muscle.
Other structures in the chest wall include ribs and intercostal muscles. If we look from the front of the chest, this is the pectoralis major muscle.
And this is the serratus anterior muscle.
T4a disease is when the tumor infiltrates the chest wall, not including only pectoralis muscle adhesion or invasion. And here, the tumor infiltrates into the serratus anterior muscle.
T4b disease is involvement of skin by the tumor.
It can present as skin ulceration or as satellite tumor nodules.
Or as edema of skin looking like an orange peel known as peau de orange.
All the skin changes should occupy less than one-third of the surface area of breast to be called as T4b. Infiltration of tumor into both, chest wall and skin, i.e., T4a and T4b both, is called T4c.
And when the breast cancer progresses very rapidly to cause diffuse erythema and edema of skin breast, involving more than one-third of the skin, then it is called as inflammatory breast cancer.
Now, we move on to the N-staging. To understand the N staging, first you have to know the local structures in that area.
In this figure, you can see the humerus, clavicle and sternum bone. This is the pectoralls minor muscle.
These nodular structures in the anterior axillary fold, are called as anterior group of lymph nodes. And along the head of the humerus are lateral group of lymph nodes. All these three groups, lateral to pectoralis minor muscle, are level 1 lymph nodes.
These present behind the pectoralls minor muscle are central, or level 2 lymph nodes. And these present medial to pectoralls minor muscle, are apical or level 3 lymph nodes.
And these, along the sternum are called as internal mammary lymph nodes.
For clinical N-staging, we have to palpate level 1 and 2 lymph nodes in axilla. If they are not palpable, it is NO. If palpable, and freely mobile, it is N1. If level 1 or level 2 lymph nodes are palpable, but they are fixed or matted, it is called as N2a. If only internal mammary lymph nodes are seen in CT scan without any level 1 or level 2 nodes, the it is called as N2b. If infraclavicular lymph nodes are involved, it is called as N3a.
If internal mammary and axillary lymph nodes both are involved that is N2a and N2b, then it is N3b.
Involvement of supraclavicular lymph nodes are called as N3c.
Now, let’s move ahead. Next comes the M-staging If the disease has spread to the distance organ it is called as M1 otherwise it is M0. This figure shows spread to both lungs in the form or multiple metastatic nodules.
And here, metastasis to the pleura has resulted in fluid collection, called as pleural effusion. This figure shows spread to the liver in form or multiple nodular deposits. And here, the cancer is spread to the adrenal gland.
Similarly, the spread may occur to brain, bones or other part of the body.
TNM Staging of Breast Cancer – Pathological
Pathological TNM Staging for breast cancer is done on surgical specimen of breast and regional lymph nodes.
Tis – Pre-cancerous changes or carcinoma in situ (CIS). No spread to nearby lymph nodes or distant body parts.
T1 – Tumor size is 2 cm or less. No spread to nearby lymph nodes or distant body parts.
T2 – Tumor size >2 cm, but </=5 cm. No spread to nearby lymph nodes or distant body parts.
T3 – Tumor size >5 cm. No spread to nearby lymph nodes or distant body parts.
T4 – Tumor of any size with direct extension to the chest wall or skin or inflammatory breast cancer.
N1 – Cancer spread to 1-3 axillary lymph nodes or tiny cancer deposits in internal mammary lymph node(s) on sentinel lymph node biopsy.
N2 – Cancer spread to 4-9 axillary lymph nodes or enlargement of internal mammary lymph node(s).
N3 – >/=10 axillary lymph nodes (>/=1 area >2 mm), or cancer spread to the infraclavicular (those under the collarbone) lymph nodes (>/=1 area >2 mm) [N3a],
Cancer spread to >/=1 axillary lymph nodes (>/=1 area >2 mm) with internal mammary lymph node(s) enlargement, or cancer spread to >/=4 axillary lymph nodes (>/=1 area >2 mm) with micrometastasis in internal mammary lymph node(s)[N3b], or
cancer spread to the supraclavicular (those above the collarbone) lymph nodes (>/=1 area >2 mm)[N3c].
M0 – No spread of the disease to distant body parts.
M1 – Cancer spread to distant organs like bones, lungs, liver, brain, etc.
Breast Cancer Staging Chart
Based on the TNM Staging discussed above, breast cancer can be classified into 4 stages as discussed below.
|0||Tis N0 M0|
|IA||T1 N0 M0|
|IB||T0-1 N1mi M0|
|IIA||T0-1 N1 M0|
|T2 N0 M0|
|IIB||T2 N1 M0|
|T3 N0 M0|
|IIIA||T0-2 N2 M0|
|T3 N1-2 M0|
|IIIB||T4 N0-2 M0|
|IIIC||AnyT N3 M0|
|IV||AnyT AnyN M1|
In addition to staging, estrogen receptor (ER), progesterone receptor (PR), HER2/neu (HER2) status, and grade of the cancer is evaluated on the surgical specimen to assess the prognosis of the disease, and planning the treatment.
Stage Grouping – Localised, Locally Advanced and Metastatic Breast Cancer
To make things easier, we stage the breast cancer into stage groups. It can broadly be divided into localized, locally advanced or metastatic disease.
Localised disease includes cases up to T2 N1 M0 and T3 N0 M0. Starting from T3 N1 M0 and onwards all N2 and N3 and T4 cases are included under locally advanced disease. Metastasis to other sites, as we have discussed previously is called M1 disease.
Survival Rate/ Life Expectancy based on Staging
- Cancer is limited to the breast.
- 5 year survival 99%.
- Cancer has spread to nearby structures or lymph nodes
- 5 year survival 86%.
- Cancer has spread to distant body parts.
- 5 year survival 27%.
Breast Cancer Staging Investigations
It uses low dose X-rays to examine the breasts. In this test, a special machine has used that consist of two plates to compress and flatten the breast to be examined. Thereafter, an X-ray image of the breast is taken. This test can provide information about the cancerous changes within the breast tissue which generally appears as a lump/mass, microcalcifications, or other changes. Any abnormality observed during this test warrants detailed investigations to establish the diagnosis of breast cancer. Mammograms are not very sensitive in case of dense breast tissue. Mammography imaging of the breast is reported as a score called BIRADS score.
- BIRADS 1 means absolutely normal breast, with 0% chances of malignancy.
- BIRADS 2 means the presence of benign findings, with 0% chances of malignancy.
- BIRADS 3 means the presence of findings that are probably benign, with less than 2% chances of malignancy. Needle testing of breast is not required in BIRADS 1, 2 or 3.
- BIRADS 4 means suspicious for malignancy, with 2-95% chances of malignancy. Needle testing should be considered in this.
- BIRADS 5 means highly suggestive of malignancy, with more than 95% chances of malignancy. Needle testing should be done in this.
Needle testing of breast may be done by FNAC or biopsy, but biopsy is preferred as it is more accurate, and provides sufficient tissue for ER, PR and HER-2 testing.
This test can distinguish between fluid-filled cysts (mostly benign) and solid tumor masses. This technique can also be used to guide a needle to collect biopsy samples.
- Biopsy sample is generally collected from the suspected areas observed during the mammography or the breast ultrasound.
- Depending on the size and location of the suspicious area, a fine needle biopsy, a core needle biopsy, or a surgical biopsy technique is utilized.
- Sometimes, a biopsy sample from lymph nodes under the arms may also be collected.
- The collected biopsy samples are examined in a laboratory and can provide information about the type of cancer, grade of cancer, and the presence of specific defective genes or proteins in the cancer cells.
- Breast cancer is classified into hormone receptor positive, Her-2 Neu positive or triple negative disease based on biopsy testing and it is very important as it determines the further treatment of the disease.
So first we did a local imaging, when we had a suspicious mass in breast. Then we did a needle testing to confirm that it is cancer. Once the diagnosis of breast cancer is confirmed, we have to do the systemic imaging depending upon clinical presentation, to stage the disease, whether it is localised, locally advanced or metastatic. Any one or more of the following investigations may be required for staging work-up of the tumor-
- Whole Body PET CT Scan
- CT Scan
- Bone Scan
- X Ray Chest
- USG Abdomen