BREAST CANCER - Article By Hina Fatima

BREAST CANCER

(Article By: Hina Fatima, 4th Year MBBS Rawalpindi Medical College)

Cancer in its numerous forms is becoming a in every dimension growing problem in our modern all providing life and lifestyle.

Cancer is defined as rapid creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs.

It is a leading cause of death and accounted for 7.6 million deaths (around 13% of all the deaths) in year 2008 according to the estimates of Global Health Observatory.

Among all the cancers, lung, BREAST, colorectal, stomach and prostate cancer cause the majority of cancer related deaths. So the cancer type which would be focussed upon in this article stands
second in cancers list.

Breast cancer though occurs in both genders but the higher risk gender is females in which it occurs a 100 times more commonly than in men. Looking at the ratios described for England and Wales (by GHO) there are 37000 new cases diagnosed and 11000 deaths recorded each year in females from breast cancer. In contrast in men there are just 270 new cases that are diagnosed and 70 deaths recorded each year….so the mark difference is evident.

Coming to our chosen cancer we give some basic knowledge about it.

Breast cancer is a cancer that starts in the tissue of breast. It generally has two main types depending on its site of origin in breast tissue. These are as follows:

1. Ductal carcinoma that starts in ducts that move milk from breast to nipple (common type).
2. Lobular carcinoma that starts in lobules- the milk producing part.

SYMPTOMS:-

Symptoms appear as the cancer advances to higher stages of its growth. These include:

1. Breast lump or lump in armpit that is hard, feels different from rest of breast tissue, non tender and has even edges.
2. Change in the size, shape and feel of the breast or nipple like redness, nipple inversion, skin dimpling or puckering that looks like skin of orange- peau de orange sign.
3. Fluid may come out of nipple which may be bloody, clear to yellow, green and pus like.

In advanced cancer there may be bone pain, breast discomfort or pain, skin ulcers, swelling of one arm and weight loss.

PATHOPHYSIOLOGY and GENETIC BASIS

Breast cancer like other cancers is a multi-factorial phenomenon that is it is influenced by both genetic and non-genetic factors like environment.

 Normally, human system and its growth processes are tightly regulated, tissues that are essentially needed divide and propagate while those either having committed their roles or are no longer needed undergo the process of apoptosis hence, ending their lives… this division and proliferation is under control of genes which are liable to be copied with errors in the progeny cells …for correcting the genetic errors there are error correcting proteins but unfortunately if these proteins are having errors themselves either inherently or later on from environmental factors they stand unable to restrain other mutations leading to uncontrolled division of cells, lack of their attachment to each other and finally their invasion of other organs-the scenario called cancer (breast cancer here).The common mutations of this repair system are those in p53 (guardian of genome from its role in conserving genome stability), BRCA1 ( care-taker gene producing breast cancer type1 susceptibility protein involved in gene repair) ,BRCA2 ( produces breast cancer type2 susceptibility protein) tumor suppressor mechanisms. 

The phenomena of apoptosis is under control of anti-apoptotic PI3K/AKT (phosphoinositide-3-kinase/protein kinase b) system and pro-apoptotic PTEN (phosphatase and tensin homolog) gene…mutations in the PTEN protein ( involved in inhibition of PIK3/AKT system and hence, is a tumor suppressing product) leads to a constant “on” position of PIK3/AKT system and hence uncontrolled cell division occurs with unwanted cells evading the process of apoptosis leading to cancerous state of breast tissue.

RISK FACTORS

FIXED

1. Age and Gender: women over 50 years of age are particularly susceptible.
2. Family History: History of breast, ovarian, uterine or colon cancers in one of the close relatives leads to increase incidence of breast cancer.
3. Genes: gene defects in BRCA1 and BRCA2 genes leads to 80% chances of developing breast cancer sometime during life.
4. Menstrual History: both the early onset of periods (before 12years of age), and late onset of menopause (after 55years of age) increase the susceptibility for developing cancer. 

MODIFIABLE

1.      Alcohol use: drinking 1-2 glasses/day increases risk for breast cancer.

2.      Child birth: women becoming pregnant more than once and before age 30 have reduced risk of breast cancer.

3.      DES: women having received diethylstilbestrol have an increased risk for breast cancer after age 40.

4.      HRT: hormone replacement therapy with a lot of exposure to estrogen for several years leads to increased chances of breast cancer.

5.      Radiations: if radiations are received in the chest area during period of breast development it may increase the risk of developing cancer of the breast.

DIAGNOSIS

Diagnosis is based on two things-one is the screening which involves approaches to early detection of presence of cancer. It consists of:

1.      Clinical and self breast exams

2.      mammography screening (recommended for women having a family history and is done early on)

3.      genetic screening

4.      CT-scan (detects local breast cancer recurrence)

5.     MRI

6.     PET-scan (to make a new diagnosis of metastases when imaging is suspicious but not diagnostic of metastases).

Now there comes the second step which is the precise diagnosis and is based on:

1.      excisional biopsy

2.      core biopsy

3.      vacuum assisted breast biopsy

4.      sentinel lymph node biopsy

      In case of advanced breast cancer recommendations are to:

1.      assess the presence and extent of visceral metastases

2.      assess the presence and extent of metastases in axial skeleton using whole body MRI if other imaging is equivocal for metastatic disease.

3.      assess for pathological proximal limb fractures using bone scintiography and/or plain radiographs

GRADING AND STAGING

Grade:

Grading compares the appearance of the breast cancer cells to the appearance of normal breast tissue. Normal cells in an organ like the breast become differentiated, meaning that they take on specific shapes and forms that reflect their function as part of that organ. Cancerous cells lose that differentiation. In cancer, the cells that would normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade) as the cells progressively lose the features seen in normal breast cells. Poorly differentiated cancers have a worse prognosis.

Stage:

Breast cancer staging using the TNM system is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.

The main stages are:

Stage 0 is a pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).

Stages 1–3 are within the breast or regional lymph nodes.

Stage 4 is 'metastatic' cancer that has a less favorable prognosis.

TREATMENT:-

Treatment is guided by the presence of 3 types of receptors on breast cancer cells; estrogen receptors, progesterone receptors, HER2/neu receptors.

ER+ cancer cells depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. tamoxifen) or by blocking production of estrogen using aromatase inhibitors (e.g anastrazole and letrozole), and generally have a better prognosis.

 HER2+ breast cancer had a worse prognosis, but HER2+ cancer cells respond to drugs such as the monoclonal antibody trastuzumab (in combination with conventional chemotherapy), and this has improved the prognosis significantly.Cells with none of these receptors are called basal-like or triple negative.

According to stages of cancer following treatment plan is recommended:

Stage1 cancers:

1.      Lumpectomy

2.      Radiation therapy

3.      Chemotherapy  (done only for HER2+ cancers with Trastuzumab.

Stage2 and 3 cancers:

1.      Surgery (lumpectomy-removal of small part of breast or mastectomy-removal of whole of breast)

2.      Radiation therapy

3.      Chemotherapy is beneficial in estrogen receptor-negative (ER-) disease. It is given in combinations, usually for 3–6 months. One of the most common treatments is Cyclophosphamide plus doxorubicin.Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT. Another common treatment, which produces equivalent results, is cyclophosphamide, methotrexate, and fluorouracil (CMF)

Stage 4 cancers

1.      Combination of different type of treatments is used.

FOLLOW UP CARE

1.      Follow up appointments scheduled for every 3-6 months

2.      Pelvic exams for post-menopausal patients receiving tamoxifen as it increases risk of uterine cancers.

3.      Bone health assessment of patients receiving aromatase inhibitors as well as those who are pre-menopausal and are receiving tamoxifen.

PREVENTION

1.        Doing regular exercise

2.        avoiding alcohol and obesity

3.        prophylactic mastectomy in women with relevant gene mutations

4.        breast awareness and self breast exam. Self exam is done in following way:

·         lie down and place your right arm under your head

·         use finger pads of 3 middle fingers of you left hand to examine the right breast. Use circular movements.

·          Use 3 different levels of pressure to examine the tissue

·         Move around the breast in an up and down pattern starting at an imaginary line drawn straight down your side from the underarm and moving across the chest to middle of chest bone. The lower extent of examination should be till you feel only the ribs and upper extent till you feel collar bone.

·         Repeat the exam on left breast.

·         Look for any change in size, contour of breast and change in color or dimpling and puckering of skin while standing in front of mirror with your hands at hips.

·         Examine each underarm while sitting up or standing with your arm slightly raised.

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