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An Approach to Breast Cancer
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An Approach to Breast Cancer

Topics / Surgery / Surgical Approaches

Basics

Anatomy

The breast is a modified sweat gland. It extends from the lateral border of the sternum to the midaxillary line and from the second to the sixth rib. The breast has an “extension” called the axillary tail of Spence which pierces the deep fascia and extends into the axilla. Each mammary gland of the breast has around 15-20 lobules which are drained by the lactiferous ducts that open separately on the nipple.
 
The Cooper’s ligaments (suspensory ligaments of Cooper) and the fibro-collagenous septa are the connective tissue of the breast that help maintain structural integrity. These ligaments extend from the posterior capsule of the breast to the superficial layer of fascia within the dermis. (Basically extend from the skin to the “back” of the breast) During pregnancy, the breast enlarges as new glandular tissue is formed and a similar phenomenon occurs during the menstrual cycles due to increments in LH and FSH. The breast is also divided into quadrants as seen on the right – the tail of Spence extending into the axilla.

1. Medial mammary branches of perforating
branches and anterior intercostal branches of the internal thoracic artery (arises from subclavian).
2. Lateral thoracic and thoracoacromial arteries (arises from axillary artery).
3. Posterior intercostal arteries (arises from the thoracic aorta in the 2nd, 3rd and 4th intercostal
space).

1. Axillary vein
2. Internal thoracic vein

1. Axillary Lymph nodes – 75% of the ipsilateral breast drains to the axillary lymph nodes. There
are 5 groups: Anterior, posterior, medial, lateral and apical lymph node group. These lymph nodes
will then drain towards the supraclavicular, infraclavicular and cervical lymph nodes.

  • The lymph nodes are anatomically divided into levels by the pectoralis minor muscle:
    • Level 1: Lateral to the pectoralis minor
    • Level 2: Posterior to the pectoralis minor.
    • Level 3: Medial to the pectoralis minor, extending up to the apex of the axilla.

2. Internal Mammary nodes – Drain 20% of the breast, especially the upper and lower inner
quadrants.
3. Interpectoral Lymph nodes – Located between the pectoralis major and the pectoralis minor
muscle

Differentials (Breast Lump)

The differentials for a breast lump can be classified according to the pain. It is important to note that breast malignancies are present more commonly as painless breast lumps.

Painless Lump Painful Lump
  1. Carcinoma
  2. Cyst
  3. Fibroadenoma
  4. Fibroadenosis
  1. Fibroadenosis
  2. Cyst
  3. Abcess
  4. Galactocoele
  5. Mastitis
  6. Fat Necrosis
  7. Carcinoma - Rare, only 10% presents with pain.

Pathology of Breast Cancer

WHO classifies breast cancers into epithelial and non-epithelial tumours. Non-epithelial tumours arise from the supporting stroma of the breast and these include angiosarcoma, malignant phyllodes tumour,s and primary sarcomas. The epithelial tumours arise from the cells lining the ducts or lobules. They can be divided into invasive and non-invasive based on the invasion of the basement membrane.

Differential for Breast Cancer
Non-Invasive Invasive
Ductal Ductal Carcinoma in Situ (DCIS) Invasive Ductal Carcinoma (IDC)
Lobular Lobular Carcinoma in Situ (LCIS) Invasive Lobular Carcinoma (ILC)
Others 1. Medullary, colloid, tubular, papillary
2. Inflamatory carcinoma of the breast (T4d).

I have omitted details concerning each of these cancers on purpose. These notes will be focusing on the clinical aspect of breast cancer and not necessarily on the in-depth details as you would have been expected to know in year III of your MBChB curriculum.

History

1. History of Presenting Complain
2. History of Risk Factors
3. History of Metastatic Work Up
4. History of Patient Operability

The presentation of the patient

Breast cancer may present as a breast lump that may be painful or painless (very important). It depends on how aggressive the tumour is; especially if it is ignored. Breast lumps are difficult to detect in large breasts. This means that in these patients breast cancer is normally present in an advanced stage.
 
The patient may also present with alveolar and nipple changes. This may have many presentations such as discharge, nipple retraction, and nipple deviation.
There may be skin changes such as:
 
  1. Erythema
  2. Peau d’ Orange – “Orange peel skin”. Caused by
    lymphatic obstruction.
  3. Ulcers
  4. Skin colour changes – Could be caused by poor
    lymphatic drainage or inflammation.
  5. Warmth of skin, Swelling.
Peau d’ Orange. From dailyrounds.org. Link provided below.

The patient may also complain of breast pain without a lump. Breast pain could be cyclical or noncyclical. Cyclical means that it follows the menstrual cycle and it is common among women. If it is non-cyclical then it usually means that there is some pathology. Breast pain is termed mastalgia or mastodynia. Mastodonia also refers to breast pain, but it may refer to breast pain in males (Mtimba L, 2018). However, the term mastalgia is the one commonly used. Non-cyclical pain is usually due to malignancy until proven otherwise.

Tethering, also known as skin dimpling may also be present. There is a dimple over the lump and this occurs because as the tumour grows, it encroaches on the connective tissue and “pulls” the suspensory ligaments of Cooper to make the appearance of a dimple over the skin. Although it is seen on the skin, it is actually NOT part of skin changes.

The most important presentation is saved for last. The patient can also be symptomatic. This presentation is common in “large – obese” patients.

The history of the Presenting Complain

You need to ask about the different types of presentations mentioned above. These questions are
simple to remember if you understand how they can present.

  1. Painless breast lump?
  2. History of nipple discharge?
    1. If present – ask about the colour:
      1. Clear – Cystic
      2. Yellow/Pus – Abscess/ Mastitis
      3. Red or pink – Ductal papilloma/carcinoma
        iv. White fluid – Galactorrhoea/Lactation
      4. Remember that during your investigations, you may want to send a sample for
        cytology/MCS. If the discharge is bilaterally it may refer to hormonal imbalances.
  3. Any skin changes?
  4. Any pain? – Remember to define if it is cyclical or non-cyclical.
  5. Areolar and nipple issues?
  6. You may ask about metastatic complains here as well.
    1. Back pain?
    2. Difficulty in breathing?
    3. Fits
    4. Headaches
    5. But this has its own section, so you don’t need to. The reason I have included it here is that in a patient with advanced breast cancer these symptoms may form part of the main presenting complaint.

 

For each of these presentations, ask about the onset, location, duration, progressiveness, is it intermittent or persistent, unilateral or bilateral, and so on.

History of Risk Factors

The risk factors could be hormonal or non-hormonal. You need to find out if your patient has any of these

1. Non-Hormonal History

  1. Being a female has an increased risk due to their breast tissue and general female behavior.
  2. Age – The older you become the higher the risk. However, malignancy in the young tends to
    be more aggressive than when you’re old.
  3. Previous history of cancer:
    1. A personal history of cancer?
    2. A family history of cancer?
      1. This is important especially if it is a first degree relative. BRCA 1 and BRCA 2 cancers are very important: Ovarian, Colon, Skin, Endometrial, and so on. Maternal side cancers are very important. The age of the family member affected by breast Cancer is also important because:
        1.  If young – hereditary (There’s a pattern in the family tree).
        2. If old – sporadic.
      2.  How to ask the questions:
        1. Do you have a history of breast cancer in the family?
        2.  Which one was it?
        3. How old was the person in your family when they had it?
  4. Radiation exposure – Had you had any history of radiotherapy?
  5. Obesity (Can also be hormonal)
  6. Alcohol
  7. Smoking
  8. Breast lesions – Fibroadenomas increase the risk.
  9. Race – White people have an increased risk but are generally detected earlier than in black
    people. Black people have a lower risk but the malignancy is detected very late and in
    advanced stages.
  10. Breast tissue density – In old women, the breast tissue density is lower than in young
    women.

2. Hormonal History

Hormonal risk factors can be grouped under:

  1. Gynecological History
  2. Past-Obstetric History
  3. Miscellaneous
Gynaecological History
  1. Early menarche (<12 years old) with late menopause (>55) is a risk factor. This is called the “Estrogen window”, what is important to know is that estrogen is a carcinogen. A prolonged exposure to it will increase the risk of malignancy.
    • Tips: A good way to ask for menopause after pregnancy has been ruled out or any other diseases: “When was your last menstrual period?”
  2. Using contraceptives – ↑ Hormones
  3. Hormone replacement therapy – These hormones should ideally not be given to a patient before consulting with a breast surgeon so that a risk assessment may be made.
  4. Other exogenous sources of hormones you can think of.
Past-Obstetric History
  1. Parity – nulliparity increases the risk.
  2. Breast feeding – Breast feeding will decrease the risk.
  3. First pregnancy – pregnancy in teenagers will decrease the risk.
    • If age of first pregnancy >25-30: ↑ risk.
    • If age of first pregnancy >30-35: ↑↑ risk.
    •  Pregnancy in advanced ages > 35-40: ↑↑↑ risk.
  4. Termination of Pregnancy(TOPS)
    •  When the breast grows during pregnancy, it occurs similar to how breast tumours
      grow during breast cancer. It grows due to hormonal exposure. If the pregnancy is
      terminated suddenly, you do not give a chance for breast development to terminate
      accordingly and hence this may increase the risk of malignancy.
Miscellaneous
  1. Obesity – The fatty tissue is able to convert androgens into estrogen by aromatization.
  2. Fatty food.

Metastatic History

  1. Weight loss and loss of appetite – Common in any malignancy.
  2. Bone pain?
    1. The most common bone pain arises in the back. This is due to vertebral
      metastases. As the tumour grows it may also compresses the nerves and leads to
      neurological issues below the level of compression.
  3. Chest
    1. Difficulty in breathing?
    2. Coughing – productive or non-productive? Breast malignancy can metastasize to the chest and cause:
      1. Ipsilateral pleural effusions
      2. Cannonball opacities
      3. Hilar lymphadenopathy
      4. Bone lesions
  4. Abdomen – a common site for metastasis is the liver. Which may result in an abnormal
    liver function. You will need to ask questions related to liver function:
    1. Tenderness?
    2. Discoloration of the skin, and mucous membranes? – Trying to rule out jaundice.
    3. Distension of the abdomen? – Trying to rule out ascites.
  5. Brain – You will need to ask questions related to the CNS.
    1. Headache?
    2. Blurred vision?
    3. Abnormal gait? Cancer can lead to leptomeningeal carcinomatosis (LC), a rare complication of
      cancer in which the disease spreads to the meninges surrounding the brain and
      spinal cord.
  6. Skin – Skin satellites.
  7. Endocrine issues – Also possible, however, the above-mentioned are the most important.

History of Operability

  1. Active person?
  2. Exercise? – Please understand that exercise is not just about going to the gym and lifting
    weights. Walking, carrying buckets of water, gardening and other activities may be
    assessed as “exercise” for the people of the community.
  3. Co-morbidities?
  4. Cough?
  5. Cardiac issues?
  6. Previous chest injuries?
  7. Difficulty in breathing lying down? How many pillows do you need?
  8. Exclude current and previous chest issues – TB? If a person had TB before, their lungs will not be functioning as well as a healthy person.

Staging

Staging is very important for any malignancy. The main reason is that staging helps us dictate the management of the person, their prognosis and it allows us to communicate with others. Each stage is treated differently the same way you treat wounds differently according to their severity. The main classification system will be the TNM staging system. You need to memorize the TNM classification and be able to stage a breast malignancy.
 
Stage 1 and Stage 2:
This is a maximum T2, a maximum N1 and a maximum M0 (T2maxN1maxM0max). So the size of the tumour must be less than 5cm, there should be no skin involment. Lymph node involment is ipsillateral axillary but mobile.When you assess the other systems there shouldn’t be any features of metastasis.
 
Stage 3:
This is a T3 and above, a N2 and above but M0 (T3≥N2≥ M0). This tumour will therefore be larger than 5cm, have skin involment or could be an inflammatory breast cancer. Lymph node involment is ipsillaterl axillary but fixed or any of the ones present at N3. However, there shouldn’t be any features of metastasis.
 
Stage 4:
This is a tumour of any size and with any lymph node involment. However, it should have the features of metastasis. It is important to realise that Stage 3 and Stage 4 are similar. The only difference is that in stage 4, metastasis is present! Hence for you to assess the pateint as having a Stage 3 Breast Cancer, you must rule out metastasis first. In order for you to stage your patient you will be required to do a physical examination. It will be divided into a Breast Examination and a Systemic Examination. The Breast Examination will assist you with the “TN” part of the system and the Systemic Examination will help you with ruling out any metastasis and hence assist you in the “M” part of the TNM classification system.
TNM Classification
Tumour Size Nodal Involment Metastasis
Tx:Tumour could not be assesed – occurs when we cannot measure the tumour or are only able to stage it radiologically instead of clinically. Nx: Nodes could not be assessed – This could be due to extrammary tissue present in the axillary tail of Spence. When the patient goes into her menses/breastfeeds the axilla becomes engourged. This prevents adequare palpation of the axilla. This can also be due to infections/skin conditions that prevent exammination. M0: No metastasis present.
Tis: Carcinoma in situ. N0: No lymph node involment. M1: Metastasis is present. This could include:
1. Bone – especially vertebrae
2. Chest –lungs
3. Abdomen – liver
4. Skin
5. Brain
T1 – less than 2cm:
a: 0.1 – 0.5cm
b: 0.5 – 1cm
c: 1 – 2cm 		N1: Ipsillateral mobile axillary lymph node involment.
T2: 2 – 5cm N2: Ipsillateral fixed/matted axillary lymph node involment.
T3: more than 5cm N3: Ipsillateral supraclavicular/infraclavicular lymph node involment or contrallaterl or internal mammary lymph node involment.
T4: Any size with chest or skin involment, or both.
a: Chest wall involment – This will include pectoralis major, serratus anterior, intercostal muscles and ribs. If it only includes the pectoralis major then it is not a T4a lesion but rather T3.
b: Skin involment – ulceration, discolorations, ulcerations, peau orange and areolar and nipple changes.
c: Chest and skin are both involved.
d: Inflammatory breast cancer
– The breast will have the typical signs of inflammation such as rubor, dolor, calor and tumor. A differential for this would be mastitis.

Physical Examination in Summary

Breast Examination

Inspection

Ask the patient to put both arms on their sides and inspect both breasts. The patient may be sitting or standing. Assess for symmetry, masses, size of the breasts, skin changes, alveolar and nipple changes, and dimpling. The patient should then be asked to lift their arms 90 to 180 degrees to assess any changes in this position.

Palpate

Palpate all the lymph nodes first. Palpate the lymph nodes of the head, neck, supra/infraclavicular, and axillary lymph nodes.
Read this part properly:

  • To examine the patient’s right axilla: Handshake your patient’s right hand with your right hand.
    Use your left hand to palpate the patient’s right axilla while letting their elbows resting on your left
    forearm.
  • To examine the patient’s left axilla: Handshake your patient’s left hand with your left hand. Use
    your right hand to palpate the patient’s left axilla while letting their elbows rest on your right
    forearm.

 

After the palpation of the lymph nodes, put the patient in a supine position. Go to the side of the pathologic breast and ask them to put their hand behind the head. This will stretch the muscles allowing you to palpate more accurately. Palpate each quadrant of the breast for any breast lumps and notice their size, location, mobility, and consistency. You may also palpate for tenderness of the breast.

Lastly, assess the nipple by asking the patient if they could squeeze them in order to observe any discharge. Remember to repeat the breast examination on the contralateral side.

Systemic Examination

In this section, you will be examining the patient in order to rule out any metastasis on a clinical basis. You will need to examine the patient for any bone pains as the malignancy of the breast commonly metastasizes to the vertebrae. Then you will need to focus on the examination of the chest (respiratory system examination), the abdomen, the central nervous system, and the skin.

At the end of the clinical examination, you should be able to say, “This is clinically a TaNbMc” or “This is a Stage 1/2/3/4 breast cancer”.

Investigations

The reasons we do investigations:

  1. To Diagnose
  2. To Stage
  3. To Assess the Operability of the patient

A breast Cancer diagnosis is done using the triple assessment. This includes:

  1. Clinical Examination (History and Physical Exam)
  2.  Imaging
  3. Histology (Tissue Diagnosis)

A.Imaging Modalities

  1. Ultrasound
  2. Mammography
  3. Breast MRI


An Ultrasound will be used for every woman, however, in women that are older than 40 years of age, mammography is added to the imaging modalities used. Women that are younger than 40 will only be investigated with Ultrasound imaging. The women that are young, pregnant, or lactating have a breast tissue density that is high. If you do mammography on these women the results of the mammography will come as very “white”, obscuring the lump that also looks “white”. Hence for these women we only use Ultrasound. Older women have a decreased breast tissue density and hence mammography can be done. In summary, we do ultrasounds on young women. We do Ultrasound and Mammography in older women.

Ultrasound Mammography Breast MRI
  • It is important for all the patients, especially in the younger women. It helps us identify:
    • 1. Consistency of the mass (solid/cystic)
    2. Localization of the mass
    3. Assess the mass in areas that mammogram cannot access, such as the axilla.
  • Ultrasound abnormal features:
    • 1. Hypoechoic lesion
    2. With hyperechoic halo
    3. Irregular edges
    4. Hypoechoic shadows
    5. It is taller than wide
    6. High central vascularity
  • Mammography abnormal features:
    • 1. Neo-densities (New areas that look “white” will be suspicious).
    2. Microcalcifications
    3. Spiculated mass/Stellate lesions
    4. Architectural distortion
  • It is very expensive, not commonly used but provides good soft tissue definition. It may be used in some scenarios. If we need to find out in which quadrant a breast cancer lesion is present in a young patient, then breast MRI can be used. You cannot use mammography in young patients and therefore a breast MRI is adequate for this scenario.

After the mammography is done, the results are given using BI-RADS. BI-RADS stands for Breast Imaging Reporting and Data System. Essentially this will tell you if it’s begin or malignant and what you should do in each case.

  • Category 0 – You need additional evaluation to assess the patient. An MRI is done next.
  •  Category 1 – Negative (Confusing but 1 is NEGATIVE, not 0)
  • Category 2 – Benign lesion. This is probably a round lesion with no margin issues.
  • Category 3 – Probable benign. However, the results don’t give you too much confidence
    and hence a short-term follow-up is suggested. These patients require a follow-up from 6
    months to 1 year. If you’re in Category 3 and have any of the conditions below, the breast
    should be removed.
    • Have a family history of breast cancer or
    • They want to get pregnant or
    • Have high risks for breast cancer or
    • The patient won’t come back for the follow us due to socio-economic reasons.
  • Category 4 – Suspicious of malignancy. A biopsy should be considered (Tru-cut).
  • Category 5 – Highly suggestive of malignancy. Do a biopsy (Tru-cut).
  • Category 6 – Known malignancy – Histologically proven malignancy. You may do it to decide
    if you want to do a wide local excision (WLE) or a mastectomy. This is when you have
    already made a diagnosis and may want to localize the lesion.

B.Tissue Diagnosis/Histology

1. Fine Needle Aspiration Cytology (FNAC or FNA)

What do you need to do for the procedure?
1. 10ml or 20ml syringe
2. Cytological fixative spray
3. Alcohol swabs to disinfect
4. Needle size for the syringe (size 22 or 21 – Black/Green )
5. 2 Microslides – One slide is fixated using the fixative spray.

The other slide is not fixated and is allowed to dry. We do an FNAC in every patient. It is the first investigation done but this cannot tell you the type of tumour. Cytology is the study of cells and hence it will not show you the basement membrane. In order for a tumour to be  invasive, it needs to invade the basement membrane. Hence this type of biopsy will not tell you if the tumour is benign or malignant. It will only tell you if the lesion has “atypical cells”. It is important to also understand that atypical cells do not always mean malignancy. FNAC does not analyze the receptor status of the cells. If the results are “atypical cells”, then you will need to do a tru-cut biopsy in order to identify if it is cancer or not. If it’s not atypical cells, then you could think of benign breast lesions like fibroadenomas.

2. Core-Needle Biopsy (Trucut)

What do you need to do for the procedure?
1. A tru-cut gun
2. Gauze swabs to clean
3. Needle size of tru-cut gun is 14.
4. Local anesthesia – This is a painful
procedure. Remember that lower
numbers are actually large needles.

A Trucut biopsy will tell you if the tumour is benign or malignant. The needle is bigger so more tissue will be collected, allowing the pathologist to assess if there is basement membrane involvement. Receptors are analyzed using a tru-cut biopsy, not in a FNAC.

3. Incisional Biopsy

Only do an incisional biopsy if there is ulceration. Do not do an incisional biopsy if there are no wounds on the breast. If there is no wound rather do an excisional biopsy. If you understood the TNM staging, this means that you will only do an incisional biopsy if the lesion is a T4b (skin involvement). In an incisional biopsy, you are cutting a wedge of tissue and using that as your sample. If there was no previous skin involvement then you have now involved the skin and upgraded it to a T4b. Therefore avoid incisional biopsy if it is not needed.

4. Excisional Biopsy

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Assess the Operability of the patient

You need to assess the operability of the patient and if they are able to undergo chemotherapy and radiotherapy. If they are unstable then they may not be able to undergo any of these procedures and you need to stabilize them first. Request the following: FBC, U/E and Creatinine, Chest X-Ray, ECG, Echocardiogram, Nutritional Status, and so on. These are some of the tests you may request for.

Management

Management depends on the stage of the patient. The stage of the patient can be divided into 3:
1. Early Breast Cancer (Stage 1 and Stage 2)
2. Locally Advanced Breast Cancer (Stage 3)
3. Metastatic Advanced Breast Cancer (Stage 4)

Early Breast Cancer Treatment

1. Surgery

In order to treat early breast cancer, you will be focusing on the breast and axilla. In each, you will
have different options for management.
→ For the breast:
1. Mastectomy with a breast reconstruction or
2. Wide Local Excision with a contralateral breast reduction

→ At the same time, you will assess the lymph nodes of the axilla for treatment. You will divide the
axilla under clinically palpable lymph nodes (N1) or clinically non-palpable lymph nodes (N0)
during the physical examination.

  • A. If clinically palpable lymph nodes (N1):
    • Do a level 2 ipsilateral axillary lymph node dissection.
  • B. If clinically non-palpable lymph nodes (N0):
    You need to do a sentinel lymph node biopsy.
    1. If the sentinel lymph node biopsy is negative:
      Close the wound you have made at the axilla and treat the patient with adjuvant radiotherapy for micrometastasis.
    2. If the sentinel lymph node biopsy is positive:
      Then this is a sign of metastasis. Do a level 2 ipsilateral axillary lymph node dissection. You treat them the same way as if they were an N1.  During this procedure, you would ideally expect to remove around 10 lymph nodes for it to be described as an “adequate” level 2 ipsilateral axillary lymph node dissection.

Wide Local Excision (WLE)

It forms part of “breast conservative therapy”. In order for a patient to have a WLE, there must be no contraindications for its use. These patients must go for adjuvant radiotherapy. If there is a contraindication for radiotherapy then these patients must go for mastectomy and not for the WLE. They may also go for chemotherapy, but radiotherapy is a must.

The indications to perform a mastectomy and WLE are the same. The contraindications for these procedures are not. If patients are not eligible for a WLE then a mastectomy is performed instead. Hence we should identify those patients who are not eligible for WLE due to contraindications.

Who cannot go for WLE:
1. Pregnant women – We cannot give radiotherapy to pregnant women and therefore a mastectomy is done instead.
2. Patients with a previous full dose of radiotherapy – Ideally you should only have radiotherapy to the same organ once. If you have radiotherapy for another cancer it should not be repeated.
3. Breast Mass Ratio – If the breasts are too small then do a mastectomy.
4. Multicentric/Multifocal tumours should not be treated with WLE.
5. Connective tissue disease.

Unlike WLE, mastectomy doesn’t always require adjuvant radiotherapy. However, it may need adjuvant chemotherapy. Adjuvant radiotherapy will be needed in mastectomies if the margins around the tumour are compromised (around less than 1cm) during a mastectomy. In that case, a re-excision of the chest wall is done. If the margins are well defined then adjuvant chemotherapy is chosen.

2. Chemotherapy and Radiotherapy

After performing surgery, a patient will be placed on adjuvant chemotherapy and adjuvant radiotherapy. The common regimes used for chemotherapy are CAF and CMF.

CAF: Cyclophosphamide, Adriamycin and 5-Flourouracil
CMF: Cyclophosphamide, Methotrexate and 5-Flurouracil

You give chemotherapy for 6 months. Each cycle will be one month. Radiotherapy is a localized therapy while chemotherapy is a systemic therapy and hence useful when there is the possibility of metastasis.

* These regimes will differ according to availability/institution. Each institution probably has its own protocols stating the duration of treatment.

3.Hormonal Therapy

In some cases, cancers have receptors for hormones and they will grow because of them. Hormonal therapy may be needed in this case. A woman’s normal source of estrogen arises from the ovaries and from the adipose tissue. Post-menopausal women don’t have functioning ovaries and hence we treat them mainly with Aromatase Inhibitors.

We mainly use two drugs: Tamoxifen and Aromatase Inhibitors.

  1. Tamoxifen: This is a weak estrogen receptor agonist. It is an Estrogen Receptor Modulator that binds to the estrogen receptors and prevents estrogen from binding to them. It does not stop the production of estrogen but rather it stops the action of estrogen. This drug can be used in pre and post-menopausal women.
  2. Aromatase Inhibitors: Androgens are converted into estrogens in the adipose tissue. The source of estrogen in older women is mainly arising from the adipose tissue. This is a good drug for them and hence is mainly used for post-menopausal women.


Hormonal therapy is given for around 5 years. It is associated with DVT and pathological fractures
so we do not want to expose women to them for a prolonged period of time. Younger patients may
not be able to fall pregnant while on these drugs so they should be counseled.

4. HER-2 Positive Breast Cancer

These cancers test positive for a protein called Human Epidermal Growth Factor receptor 2, which promotes the growth of cancer cells. They are less likely to respond to hormonal therapy since they depend on other sources for their growth. HER-2-positive breast cancers are more difficult to treat. To treat these malignancies you give antibodies such as Herceptin which will bind to these
receptors. Give Herceptin for 1 year.

It is important to understand that hormone receptor-positive breast cancers are actually less aggressive than if they were receptor-negative. HER-2 receptor-positive malignancies are actually more difficult to treat – more aggressive.

5. Follow Up

This is the last part of early breast cancer treatment. You will ideally want to do a clinical breast exam yearly and mammography.

Advanced Breast Cancer Treatment

This is made up of locally advanced (stage 3) and metastatic advanced breast cancer(stage 4). As we have already mentioned, stage 3 is diagnosed by excluding stage 4. This is done by ruling out metastasis. Essentially Stage 4 is a confirmed M1 and Stage 3 is an excluded M1.

  • Stage 3: T3 or more, N2 or more, and M0.
  • Stage 4: Any T, Any N, and M1.

Therefore we must do a metastatic workup to differentiate between M0 and M1

Hormonal Therapy

Remember that bones are the commonest site for metastasis. You will need to do the following investigations:

  1. Bone scan – Detects metastasis even if the patient is asymptomatic.
  2. PET scan – glucose uptake by cancer cells may be detected.
  3. Chest X-Ray – Will show ipsilateral pleural effusions, Cannonball opacities, Hilar
    lymphadenopathy or bone involvement.
  4. Abdominal Ultrasound – Assess liver metastasis.
  5. Then investigate per symptom. Only do a CT Brain if they are symptoms of confusion,
    headaches or visial problems.
  6. Remember that you may use your History of metastasis to evaluate which tests you want to
    request.

If there is no metastasis then you treat the patient for Stage 3 Breast Cancer, otherwise, Stage 4 treatment will be used.

Stage 3 Treatment

The treatment is surgical. You will first give the patient neoadjuvant chemotherapy for 6 months (6 cycles). When you give neoadjuvant chemotherapy the tumour will respond in different ways and we group our patients accordingly.

  1. Complete response: In these patients, the tumour has disappeared.
  2. Partial response: In these patients, the tumour has reduced in size by more than 50% of its
    original size.
  3. Poor response: In these patients, the tumour has not reduced more than 50% of its original
    size.

Patients with a “Complete response” and a “Partial response” are treated with a mastectomy and a level 2 ipsilateral axillary lymph node dissection. Patients with a “poor response” are placed on second-line chemotherapy drugs.

After the second-line chemotherapy drugs, the tumour will have a different response. It will either:

  1. Decrease in size so that you may be able to perform a mastectomy with level 2 ipsilateral axillary lymph node dissection OR
  2. Doesn’t decrease in size (poor response) and you will need to treat them with palliative care.

Stage 4 Treatment

These malignancies have no cure, so we do palliative treatment. We divide these patients as:

  1. Short-term survivors
  2. Long-term survivors

Treatment for Long-Term Survivors

These patients will survive up to 2 years. They may have lung or bone metastasis. The treatment will depend if the maligncy is either:

  1. Hormone Receptor Expressing:
    → Treat with Hormone Therapy as a first-line drug and chemotherapy as a second-line drug if there is no response. OR
  2. Non-Hormone Receptor Expressing:
    → First line is chemotherapy.

Treatment for Short-term Survivors

These patients will survive less than 2 years. They present with brain and liver metastasis as well as pleural effusions. First-line therapy is chemotherapy. If the patients have brain metastasis, then include external beam radiation. If the patients have bone pain include radiotherapy to the areas of pain.

These patients will lose Ca+2 from the bones so give them bisphosphonates which will bind to the surface of bones and slow down the bone resorption action of osteoclasts. This allows osteoblasts to work more effectively.

Published on September 5, 2022
Dr RW Becerra Estevez
Dr RW Becerra EstevezMBChB (WSU)

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