Different Ways Of Testing For Breast Cancer Biology Essay

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The breasts are a special organ in females because they are the visible symbol of their femininity & they are responsible for feeding of newborn child. Cancer is a malignant tumor which means that cells are dividing uncontrollably & keep dividing even though new cells are not needed. Breast cancer is only one of 200 different types of cancer. Every year more than 200,000 women are diagnosed with breast cancer. It is a very serious disease that occurs commonly in females but can occur also in males. It is the commonest cause of death in middle aged females because it discovered in late stage. The incidence of breast cancer is one out of nine women. It is more common in western countries & rare in Japan.

The New York Times said that breast cancer is caused by many factors; the 1st factor is genetic factor which accounts for 5 - 8% of cases. There is gene called Breast cancer (BRCA) gene which is located on chromosome 17, if mutation occurs to this gene it will lead to breast cancer in young age.

The 2nd factor is hormonal factor which caused by prolonged exposure of breast to estrogen as in early menarche, late menopause, nulliparity, oral contraceptive pills (OCP), hormonal replacement therapy (HRT) & having first child at a late age. This factor can be protected by multiparity, having 1st child at an early age & breast feeding.

The 3rd factor is familial factor which increased the risk if one of the 1st degree relatives has breast cancer.

The 4th factor is socio-economic factor which is more common in high classes but in lower classes tend to present with late stage.

There are also other factors as radiation, nutrition, obesity & atypical epithelial hyperplasia. (The New York Times, Breast cancer, From the World Wide Web http://health.nytimes.com/health/guides/disease/breast-cancer/overview.html)

He said that the pathology of disease arises from the epithelium of the terminal duct lobular units (TDLU), which is in the breast lobule. It may be carcinoma in situ or invasive carcinoma.

The carcinoma in situ is limited to the basement membrane, it used to be rare but it is becoming increasingly common phenomenon with the advent of mammographic screening. There are 2 types; the 1st type is ductal carcinoma in situ (DCIS), it accounts for 4% of symptomatic cases & 25% of screen detected cancer. It is large irregular cells with large irregular nuclei limited by basement membrane. DCIS

It includes 2 types; Comedo DCIS & Non-Comedo DCIS. The 2nd type is lobular carcinoma in situ (LCIS), which is usually an incidental histological finding less than 1% of symptomatic cases & 1% of screen detected cancer. There is expansion of breast lobules by small regular cells with regular oval nuclei with intact basement membrane. It tends to be multifocal & bilateral. These patients are managed by observation not by surgery.

Invasive breast carcinoma has 2 types; invasive duct carcinoma or non special type accounts for 80% of cases & invasive lobular carcinoma accounts for 10%.

Special type of invasive carcinomas accounts 10% & are better prognosis. They include tubular carcinoma, colloid carcinomas & medullary carcinoma.

Inflammatory carcinoma is a rare type which is highly aggressive cancer presents with painful swollen, warm breast & skin edema. The biopsy will confirm the diagnosis & show undifferentiated carcinoma cells. It used to be rapidly fatal but nowadays with aggressive chemotherapy & radiotherapy the prognosis is much better.

Paget's disease of the nipple is superficial manifestation of an underlying breast carcinoma. It presents as eczema like lesion of nipple & areola which persists despite local treatment. It is slowly erodes nipple which will eventually disappear. If we take biopsy from nipple it will show large ovoid cells with clear cytoplasm in epidermis. (Bailey & Love's, 24th Edition, P. 840 - 844)

He said that breast cancer can spread by many ways, as local spread (tumor increase in size & tend to involve skin & penetrate pectoral muscles), lymphatic spread (to axillary lymph nodes) & bloodstream spread (to bones, liver, lungs & brain). (Bailey & Love's, 24th Edition, P. 837)

Wikipedia said that the clinical presentations of breast cancer can divided into commonest presentations & presentation of advanced cases.

The commonest presentations include swelling (usually in upper lateral quadrant with tethering of overlying skin), nipple may be indurate or elevate & axillary lymph nodes may be palpable.

The presentations of advance cases include that swelling become large in size more than 5 cm & fixed to pectoral fascia or chest wall. Peau d´orange (means orange skin) which is due to cutaneous lymphatic edema; infiltrated skin is tethered by sweat ducts & so can't swell at these points. Cancer-en-cuirasse is due to direct infiltration of skin of breast & chest wall which become hard, leathery & pigmented. Lyphedema of upper limbs with recurrent attack of lymphangitis, ulceration, fungation of tumor, signs of metastasis. Peau d´orange

The patient may present for the 1st time with advanced local diseases or symptoms of metastatic disease which accounts for 20% in developing countries while 5% in developed countries. The patient may present as inflammatory swell in inflammatory carcinoma, bleeding per nipple is due to carcinoma or erosion of nipple (Paget's disease). (Wikipedia, 2010, Breast cancer, from the World Wide Web http://en.wikipedia.org/wiki/Breast_cancer)

The diagnosis of breast cancer is done by triple assessment which is a combination of clinical assessment, radiological imaging & pathological assessment. It's done for all females presented with a breast lump or other symptoms suspicious of carcinoma. The positive predictive value (PPV) of this combination should exceed 99.9%. The clinical assessment done by taking proper history from the patient as patient's age, age at menarche & menopause, family history of breast cancer, number of children, age at 1st child birth, drug history as OCP & HRT, duration & progressive of the lump. The clinical assessment also include proper examination by inspection (examine both breast at the same time, notice skin tethering or dimpling) & by palpation (palpate each quadrant to look for a lump & then palpate both axilla & supraclavicular fossa for lymph nodes enlargement). The radiological imaging done by ultrasound in females less than 35 years old, if there is suspicion we do magnetic resonance mammography. In females more than 35 years old we do mammography. The pathological assessment is done 1st by fine needle aspiration cytology (FNAC), if there is a cyst it will be cured but if the fluid withdrawn is bloody or a lump is persist it must be removed. If the cytology is inadequate or unhelpful then we do core biopsy.2.jpg 3.jpg

FNAC Core Biopsy



He said, "Clinical staging of breast cancer includes 2 systems:

§ TNM (Tumor, Nodes & Metastasis) system §



1ry tumor can't be assessed.


No evidence of 1ry tumor.


DCIS, LCIS or Paget's disease with no tumor.


Less than 2 cm.


2 - 5 cm.


More than 5 cm.


Tumor of any size with extension to the chest wall, Peau d´orange, ulceration of the skin, Seattle skin nodules or inflammatory carcinoma.



No lymph nodes metastasis.


Metastasis to mobile ipsilateral lymph nodes.


Metastasis to fixed ipsilateral lymph nodes.


Metastasis to ipsilateral internal mammary lymph nodes.



No distant metastasis.


Presence of distant metastasis.

Palpable ipsilateral supraclavicular lymph nodes

§ Manchester system §: Includes 4 stages:

Stage I (Tis or T1-2, N0, M0): There is a lump in breast with slight attachment to the skin with no palpable lymph nodes & no distant metastasis.

Stage II (T1-2, N1, M0): There is a lump attached to the skin, nipple & retro-areolar with mobile lymph nodes in axilla & no distant metastasis.

Stage III (T2-4, N2-3, M0): There is a lump with extensive involvement of the skin or Peau d´orange or adherent to the underlying muscles with fixed lymph nodes in the axilla & no distant metastasis.

Stage IV (T1-4, N1-3, M1): There is distant metastasis in the liver, lungs, bones or palpable supra-clavicular or contra-lateral axillary lymph nodes." (Abu Zaid, 2009, P. 16).

Wikipedia said that the prognosis of breast cancer depends on many factors at the same time. It include the age of the patient (if less than 35 years indicate poor prognosis), the tumor size (the larger the tumor, the poor will be the prognosis), the axillary lymph nodes metastasis (if there aren't metastasis to them indicate good prognosis & if there is involvement of more than 10 lymph nodes indicate poor prognosis), the tumor grade & the receptor status (as estrogen receptor, progesterone receptor & HER-2/neu). (Wikipedia, 2010, Breast cancer, from the World Wide Web http://en.wikipedia.org/wiki/Breast_cancer)

American cancer society said that carcinoma of the male breast accounts for less than 2% of all cases of breast cancer. The known predisposing causes include gynaecomastia (hypertrophy of the male breast may be unilateral or bilateral) & excess endogenous or exogenous estrogen. As in females, it tends to present as a lump. There are many types of breast cancer in men as infiltrating ductal carcinoma (IDC) which is the most common type, infiltrating lobular carcinoma (ILC), ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) & Paget's disease of the nipple. (American cancer society, 2010, Breast cancer in men, from the World Wide Web http://www.cancer.org/cancer/breastcancerinmen/detailedguide/breast-cancer-in-men-what-is-breast-cancer-in-men.)

He said that the treatment of breast cancer has two basic principles of treatment are to reduce the chance of local recurrence & the risk of metastatic spread. There are different types for treatment of breast cancer. The surgical treatment includes:

1- The breast conservative surgery done for carcinoma in situ & in invasive carcinoma when it is less than 4 cm in diameter. There are 3 forms:

a- Lumpectomy is excision of the tumor with 1 cm margin clearance.

b- Segmentectomy is excision of the tumor with 1 cm macroscopic margin clearance but with excision of tissue from the nipple to periphery of the breast.

c- Quadrantectomy is removal of the entire ¼ of the breast containing the 1ry carcinoma with 2-3 cm macroscopic margin clearance.

Contraindication of this surgery is:

1- Multi-factorial disease in the same ¼.

2- Multi-centric disease in separate ¼.

3- Extensive in situ component > 25%.

4- Pregnancy as radiotherapy is contraindicated except in the 3rd trimester when irradiation can be given after delivery.

5-History of previous irradiation to breast (can't repeat the irradiation).

6- Large sized tumor in small breast.

7- Presence of scleroderma or collagen disease.

8- Centrally placed tumors.

2- Modified radical mastectomy: its incision is elliptical & transverse containing nipple, areola & skin over the tumor. The whole breast & underling pectoral fascia are removed together with fat in axilla & all axillary lymph nodes in one pack. The injury of nerve to serratus anterior should be avoided which will lead to winging of scapula. A suction drain is left at the end.

3- Simple mastectomy (total): it is indicated in DCIS. It's done by removal of all breast tissue & nipple-areola complex presenting pectoral muscle & axillary lymph nodes.

4- Sentinel lymph node biopsy: sentinel lymph node means 1st lymph node draining tumor-bearing area. If sentinel node is negative for metastases, the patient is spared of axillary lymph node dissection & its morbidity (lymph-edema). But if sentinel node is positive for metastases the axillary lymph nodes dissection is done (20-25 lymph nodes is removed).

5- Breast reconstruction after mastectomy: either immediate or delayed. In early cases immediately is done but in advanced cases is delayed for 6 month after completion of adjuvant therapy.

The radiotherapy is always done after conservative surgery to decrease the risk of local recurrence. After mastectomy, it is only done in the following conditions:

1- Grade 3 tumor.

2- Extensive lymph node involvement (≥ 4 lymph nodes).

3- Extensive lymphovascular invasion.

It is done only to the chest (not the axilla which leads to sever lymphedema) & usually given after chemotherapy.

The adjuvent systemic therapy consists of chemotherapy & hormonal therapy. Its objective is to treat & eradicate occult distal metastases, delaying relapse & prolonged survival. It's improved relapse free survival by 30% & improves absolute survival by 10% at 15 years. It depends on lymph nodes status (positive or negative), grade of malignancy & receptor status (estrogen receptor, progesterone receptor & over expression of HER-2/neu). The guidelines for systemic treatment are:

A- Node-negative early breast cancer:

1- Low risk gives hormonal therapy.

2- Intermediate risk gives hormonal therapy with or without chemotherapy.

3- High risk gives hormonal therapy & chemotherapy.

B- Node positive early breast cancer: if estrogen &/or progesterone receptor negative give chemotherapy & if estrogen &/or positive give hormonal therapy & chemotherapy.

Made of chemotherapy &/or hormonal therapy:

A- Adjuvant endocrine therapy indicated in patients who are positive for estrogen receptor with or without progesterone receptor:

1- Tamoxifen is anti-estrogen which blocking estrogen receptors. The dose is 20 mg/day for 5 years given to premenopausal & postmenopausal females. Its advantages include decrease recurrence by 25%, decrease death by 17% & decrease risk of contra-lateral breast carcinoma by 50%, gives protection against osteoporosis & decrease blood cholesterol. In surgically unfit elders & in cases of inoperable cancer that are estrogen receptor positive tamoxifen is given as neoadjuvent therapy to render tumor operable (response 75%). The adverse effect is endometrial hyperplasia so may induce endometrial carcinoma.

2- Aromatase inhibitors are block conversion of peripheral androgens to estrogen. They include Anastrazole 1 mg/day, Letrozole 2.5 mg/day. It is mainly effective in post menopausal females & better than tamoxifen. They may be given after 2-3 years of tamoxifen therapy.

3- Ovarian ablation by oophectomy which decrease the risk of tumor recurrence & death in females < 50 years. It's done either by surgically (laparoscopically), or by irradiation to pelvis, or chemically by giving latinizing hormone releasing hormone analogues (LNRH).

B- Adjuvent chemotherapy can decrease the risk of cancer recurrence by 25% & annual risk of death by 25-30%. The benefit is for both patients who are node positive & node negative. The regimens used are:

1- CMF: which is Cyclophosphamide, Methotrexate & 5-Flurouracil in 6 cycle.

2- AC: which Adriamycin & Cyclophosphamide in 4 cycles.

3- EC: Epirubicin & Cyclophosphamide in 4 cycle.

Both Adriamycin & Epirubicin are anthracyclin & best given in high risk patients but they are toxic to the heart. The recent trials have shown that adding Taxane to AC regimen improves disease free & overall survival by 20%. In patients with metastasis disease & HER-2/neu positive Trastuzumab is given but is very expensive & still under trial. Adjuvant chemotherapy is considered for all node positive cancer, all cancer >1 cm in diameter & all cancer <0.5 cm & associated with bad prognostic feature as high histological grade, high nuclear grade, lymphovascular invasion negative estrogen receptor & progesterone receptor status & HER-2/neu over expression. (Bailey & Love's, 24th Edition, P. 840 - 844)

He said that management of different problems in breast cancer:

1- Suspicious lesion on mammography we do excision biopsy after localization which is done by a wire hook. Its tip is positioned close to the lesion. A 1 cm core of the breast tissue around the wire & its tip is excised. Before leaving theatre, specimen radiography is performed to confirm complete excision of the suspicious lesion.

2- In situ breast cancer:

a- Lobular carcinoma in situ (LCIS) nowadays it is considered a marker for increase risk rather than inevitable precursor of invasive disease. The treatment is observation with or without Tamoxifen (if estrogen receptor is positive). The goal is to prevent or detect at an early stage, the invasive cancer that subsequently develops in 25% of cases.

b- Ductal carcinoma in situ (DCIS) if low grade DCIS of solid, cribriform or papillary type which is >0.5 cm we do lumpectomy alone but if large DCIS lumpectomy & radiation therapy. If multi-centric DCIS (2 cm more quadrants) we do mastectomy. The adjuvant Tamoxifen is considered for all DCIS patients. In recurrence cases do mastectomy.

3- Early invasive breast cancer (T1 & T2) if the tumors >4 cm in good sized breast we do conservation surgery (lumpectomy, segmentectomy or quadrantectomy) followed by irradiation. If lymph nodes are palpable, axillary lymph nodes dissection is done but if lymph nodes aren't palpable, do either:

a- Blind axillary lymph nodes dissection.

b- Sentinel lymph nodes biopsy & if it is negative then patient can be spared axillary lymph nodes dissection & its morbidity (lymph-edema of the arm & recurrent attack of lymphangitis).

4- Advanced loco-region breast cancer (T2, T3 & N1) we do modified radical mastectomy, post-operation radiation, chemotherapy & hormonal therapy.

5- T4 tumors (T3-4, N1-2 & M0) are initially inoperable. They are treated at 1st by neo-adjuvant chemotherapy & hormonal therapy. They may become operable & surgical treatment is carried out followed by adjuvant therapy. Before treatment, bone scan & liver scan must be done to exclude metastasis.

6- Metastatic breast carcinoma is treated palliative by neo-adjuvant therapy:

a- Start with hormonal therapy if estrogen receptor & progesterone receptor are positive.

b- Systemic chemotherapy is indicated for females with negative estrogen receptor & progesterone receptor.

c- Patients with HER-2/neu over expression Trastuzumab.

Patients may develop anatomically localized problems which will benefit from individualized surgical treatment (e.g. brain metastasis, pleural effusion, pericardial effusion, biliary obstruction, spinal cord compression, painful bone metastases or pathological fracture.

7- Loco-regional recurrence includes 2 groups:

a- Female with previous breast conservation mastectomy is done & may be associated with reconstruction followed by chemotherapy & hormonal therapy.

b- Female with previous mastectomy should undergo surgical resection & appropriate reconstruction followed by chemotherapy, hormonal therapy & adjevant radiotherapy to the chest wall if it wasn't given before.

8- Inflammatory breast carcinoma characterized by skin change of brawny indurations, erythematic with raised edge & edema (Peau d´orange). It may associated with breast mass. It can be easily mistaken for bacterial infection of breast. There are palpable hard axillary lymph nodes & there may be distant metastases. It used to be fatal but nowadays neoadjuvant chemotherapy with Adriamycin containing regimen may affect dramatic regression in 75% of cases. It may be followed by modified radical mastectomy & radiotherapy to chest well & supra-clavicular fossa. (Abu Zaid, 2008, P. 24 - 25)