How a Patient with Breast Cancer Presents?
To further understand the disease in a better way, have a look at the video below where CancerBro meets Mrs. Brooks who is a 55 years old lady who has recently being diagnosed with breast cancer.
Awareness of the Risk Factors for Breast Cancer
Mrs. Brooks had a lot of risk factors for breast cancer.
The first one is the late age of marriage and first childbirth after 30 years of age, increases the risk of breast cancer.
Inadequate breastfeeding also increases the risk of the disease.
Early menarche, late menopause, and intake of hormonal replacement therapy after menopause, further aggravates the risk of breast cancer.
Previous history of breast cancer in family may also increase the risk in other family members.
Previous history of radiation exposure to chest wall, especially at a younger age, may also increase the risk of developing breast cancer.
Previous history of benign breast disorders, may further increase the risk.
A lot of cases of breast cancer can be prevented if the risk factors are kept in mind.
Awareness of the Symptoms of Breast Cancer
- Lump/Thickening/Deformity in breast or in the axilla
- Change in size and/or shape of breast
- Nipple retraction
- Nipple discharge, especially if it is bloody
- Scaly/red skin on the breast, nipple or areola
- Orange peel appearance of skin of breast (peau de orange)
- Dimpling/puckering/tethering of skin of breast
Awareness of Investigations for Diagnosis and Staging of Breast Cancer
In this video, CancerBro will explain the process of how breast cancer is diagnosed.
Imaging for breast cancer requires local imaging of the breast, and in some cases, whole body imaging called as systemic imaging.
Mammography is done in all the cases of breast cancer. In some cases, mammography may be inadequate, when ultrasound or MRI of the breast may be required.
In advanced disease or symptoms related to distant organ involvement, systemic imaging may be required, such as whole-body CT scan, bone scan, MRI brain or PET CT.
Mammography imaging of the breast is reported as a score called BIRADS score.
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.
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.
This completes the diagnostic workup for breast cancer.
Awareness of TNM Staging of Breast Cancer
The staging of breast cancer is called TNM staging. We will discuss this in detail. 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.
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.
What is 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.
Awareness of Treatment of Breast Cancer
Localised Breast Cancer Treatment
If we see the localised disease in detail, it includes cases till T3, that is tumor more than 5 cm but not infiltrating the skin or chest wall, or N1, that is presence of mobile axillary lymph nodes.
In early stage disease, the decision to move ahead with BCS depends on patient as well as oncologist. The patient has to be willing for it and give consent for the same, and oncologist has to look for any contraindications for the procedure. If everything is in favor, and the tumor size is small, breast conservation surgery maybe done directly.
Whereas if the tumor is large, we first have to give neo-adjuvant chemotherapy to shrink the tumor, and then reassess for breast conservation surgery, depending upon the response to chemotherapy.
So, the decision to add chemotherapy in the neoadjuvant or adjuvant setting is taken on an individual patient basis, after discuss in a tumor board. Also the decision to add hormonal therapy and targeted therapy is taken depending upon the ER, PR and her-2 receptor status and along with other factors.
After Breast Conservation Surgery, radiation therapy is given in all the cases. Where as after modified radical mastectomy, the decision to add radiation therapy is taken by the radio oncologist depending upon the T-status, N-status, margins of resection along with other factors.
Locally Advanced Breast Cancer Treatment
Locally advanced breast cancer includes cases with a T4 disease, that is infiltration of the chest wall or skin or N2 or N3 disease, that is, fixed or matted axillary lymph nodes.
This figure shows T4 disease, with infiltration into the chest wall or skin, and N2 or N3 disease, with a presence of matted or fixed axillary lymph nodes.
These cases are not upfront resectable.
That is why, neoadjuvant chemotherapy, that is, chemotherapy before surgery, is required in almost all the cases of locally advanced breast cancer.
One exception is T3N1 disease, that may be upfront resectable, but neo adjuvant chemotherapy may be required in these cases if planning for breast conservation surgery, in these cases.
In locally advanced disease also, the decision to do BCS or MRM is taken after neoadjuvant chemotherapy, depending upon the response to chemotherapy, as we have discussed previously for localized disease.
So the decision to add neoadjuvant or adjuvant chemotherapy is taken in an individual basis, after discussion in the tumor board. The decision to add hormonal therapy or targeted therapy depends upon the ER, PR and HER-2 status, as we discussed previously for localized disease.
Radiation therapy is required in almost all cases of locally advanced disease but the final decision is taken by the radiation oncologist by completely assessing the patient.
This brings us to the end of treatment for locally advanced breast cancer.
Metastatic Breast Cancer Treatment
Metastatic disease constitutes for 5-10% of the cases of breast cancer.
The treatment options for metastatic breast cancer are chemotherapy, hormonal therapy for ER PR positive disease, and anti Her-2 therapy for Her-2 positive disease. Radiotherapy or surgery may be added for palliation, i.e., reduction of symptoms, and bone redirected therapy may be given in presence of bone metastasis.
Remember cure is not the intent for giving treatment in metastatic disease. It is mainly given to prolong the life, reduction of symptoms, and improvement of quality of life. Treatment for metastatic disease is decided based on the site of metastasis, previous treatments taken, ER, PR, HER-2 status, performance status of the patient and the comorbidities in the patient.
What is Triple Negative Breast Cancer?
Normally, breast cancer cells have specialized proteins on/in their surface, called receptors. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are most common receptors detected on breast cancer cells, which can promote the growth of these cells.
Conversely, the drugs that inhibit these receptors are utilized to retard the growth of these cancer cells. TNBC cells do not have any of these receptors, that is, negative for ER, PR, and HER2. These breast cancers grow and spread more rapidly than receptor-positive breast cancers and do not respond to treatment generally employed for receptor-positive breast cancers, that is, hormonal or trastuzumab-based therapies.
Breast cancer is the most common cancer in women worldwide and is responsible for most cancer-related death in women. TNBC is the most aggressive subtype of breast accounting for about 15–20% of all cases of breast cancer but comparatively higher percentage of death related to breast cancer.
TNBC tends to grow and spread quickly to distant body parts, especially visceral organ (as opposed to normal breast cancers that most commonly spread to bones), making them more difficult to treat.
TNBC is not a single entity and includes many heterogenous cancer types. Based on gene expression profiling and preferred treatment approach TNBCs are divided into four subtypes: basal-like 1 (BL1), basal-like 2 (BL2), luminal androgen receptor (LAR) and mesenchymal (M) type.
These subtypes may occur individually or concurrently making it more difficult to treat TNBCs with a single targeted treatment in every patient. Thus, identification of biomarker involved in the TNBC is vital for selection of an appropriate treatment strategy.
Triple Negative Breast Cancer Treatment
The treatment of TNBC depends on many factors including the overall stage assigned to the disease, the subtype/biomarkers of TNBC involved, and the patient’s overall health & personal preferences.
The most commonly employed systemic neoadjuvant chemotherapy include anthracycline- and taxane-based chemotherapy. Addition of carboplatin to standard chemotherapeutic regimen has been reported to improve the outcome in TNBC patients and is generally recommended.
Poly (ADP-ribose) polymerases (PARPs) inhibitors are considered the first-line systemic therapy for BRCA-positive TNBC. Addition of PARP inhibitor to standard neo-adjuvant chemotherapy has been reported to improve outcome in TNBC patients with a mutation in the BRCA gene (10%-20% of all TNBC cases).
Similarly, many other targeted therapies have been tested in various clinical research studies and have shown better outcome in TNBC patients with specific genetic abnormality. The following table lists potential targeted therapy for the four TNBC subtypes with characteristic genetic alterations:
|TNBC subtype||Common genetic abnormality||Potential targeted therapy|
Cell cycle genes
DNA damage repair genes
PARP inhibitors (e.g. olaparib, talazoparib, veliparib, rucaparib, and niraparib)
Cyclin dependent kinase (CDK) inhibitors (e.g. dinaciclib, palbociclib, abemaciclib, and LEE011)
Growth factor signaling (epidermal growth factor [EGF], IGF1, MET, Wnt/b-catenin pathways)
Growth factor receptors (EGFR, IGF1R, MET, EPHA2)
Glycolysis and gluconeogenesis
Mammalian target of rapamycin (mTOR) inhibitors (e.g. everolimus, temsirolimus, ridaforolimus, and zotarolimus)
Growth factor inhibitors (e.g. Alofanib, Lucitanib)
A combination of EGFR tyrosine kinase inhibitors (TKIs) (e.g. erlotinib and lapatinib) and the monoclonal antibodies (e.g. cetuximab and panitumumab)
|LAR||Luminal gene expression; Androgen receptor gene||Anti-androgens (e.g. enzalutamide, bicalutamide, and dehydroepiandrosterone [DHEA]), Histone deacetylase (HDAC) inhibitors (e.g. Panobinostat, Entinostat, vorinostat, and Valproic Acid), Heat shock protein-90 (Hsp90) inhibitors (e.g. Ganetespib and Onalespib), Src inhibitors (e.g. Dasatinib and Saracatinib), Phosphoinositide 3-kinase (PI3K) inhibitors (e.g. taselisib, buparsilib)|
Epithelial-mesenchymal transition (EMT)
Cell motility and differentiation
Regulation of cancer stem cells
Growth factor signaling
|Drugs targeting pathways involved in EMT: Notch, Wnt/β-catenin, Hedge-hog, and TGF-β signaling pathways|