1 in 8 women in the US have breast cancer symptoms. Awareness regarding disease can help provide breast cancer treatment to more women and avoid complications.

Breast Cancer

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ZAKA CLINIC GULBERG LAHORE

Saad Ullah Siddiqui

Overview

According to the International Agency for Research on Cancer (IARC), female breast cancer has overtaken <a href="https://merisehat.pk/disease/lung-cancer-67">lung cancer</a> as the most commonly diagnosed cancer type in the world<a href="#accordion">[1]</a>. It is the leading cause of cancer-related death among women.

Although developed countries have a higher incidence of breast cancer, the mortality rate has progressively increased in developing nations. This is likely due to the lack of awareness and effective screening programs in low- and middle-income countries.

In 2020, breast cancer accounted for 14.5% of all new cancer cases in Pakistan, among both men and women<a href="#accordion">[2]</a>. Moreover, the country continues to have the highest incidence of breast cancer in Asia. 
&nbsp;

Breast cancer is of several types and is categorized based on whether they are invasive or non-invasive. 
&nbsp;

<ul>
	<li>Ductal Carcinoma In Situ (DCIS):&nbsp;Also called Stage 0 breast cancer, DCIS is non-invasive and begins in the duct cells of the breast.&nbsp;</li>
	<li>Lobular Carcinoma In Situ (LCIS):&nbsp;This precancerous condition develops in the lobules of the breast and, similar to DCIS, does not infiltrate surrounding cells. It most commonly occurs in women aged 40-50 years.</li>
	<li>Invasive Ductal Carcinoma:&nbsp;This is the most common breast tumor. It usually begins in the milk ducts and then spreads via the lymphatics to other parts of the body.&nbsp;</li>
	<li>Invasive Lobular Carcinoma:&nbsp;Cancer begins in the lobules of the breast and spreads to surrounding tissue.</li>
	<li>Angiosarcoma:&nbsp;This type of cancer is rare and starts in the cells lining blood vessels or lymphatic vessels in the breast.&nbsp;</li>
	<li>Paget Disease Of The Nipple:&nbsp;It accounts for only 1-3% of all breast cancer cases<a href="#accordion">[7]</a>. Cancer begins in the ducts and spreads to the nipple and areola.&nbsp;</li>
	<li>Phyllodes Tumor:&nbsp;They are mostly benign and develop in the breast&#39;s connective tissue.&nbsp;</li>
	<li>Triple-Negative Breast Cancer:&nbsp;Only 10-15% of people are affected by this tumor<a href="#accordion">[5]</a>. The highly aggressive cancer is characterized by the absence of three markers - estrogen receptors, progesterone receptors, and HER2 (human epidermal growth factor receptor 2) proteins. These cancers are highly difficult to treat and grow at a much faster rate than others.&nbsp;</li>
	<li>Inflammatory Breast Cancer:&nbsp;Although rare, aggressive cancer can progress very quickly. It causes the breast to swell as the cancer cells block the lymph nodes near the breasts. The breast looks inflamed and can also appear pitted like an orange peel. 
	&nbsp;</li>
</ul>

Signs And Symptoms

Most cases of breast cancer begin with a painless lump or thickening of the breast. Approximately 90% of breast lumps are benign and can result from cysts or fibroadenomas<a href="#accordion">[4]</a>. However, the presence of the following symptoms can point to a cancer diagnosis: 
&nbsp;

<ul>
	<li>Sudden change in shape, size, or appearance of the breast</li>
	<li>The lump or pain does not alter with the menstrual cycle</li>
	<li>Redness and swelling of the breast or the nipple</li>
	<li>Discharge from the nipple containing blood or clear fluid</li>
	<li>Inverted nipple</li>
	<li>Skin surrounding the nipple or breast begins to peel, scale, or crust</li>
	<li>The skin over the breast becomes red and takes on a dimpled appearance (like an orange peel)</li>
	<li>Enlarged lymph nodes under the arm or collar bone 
	&nbsp;</li>
</ul>

Causes

Breast cancer arises from cells of the breasts, most commonly the cells lining the ducts or lobules (part of the breast where milk production takes place). These cells mutate and grow at an uncontrollable rate, resulting in a tumor. Often, these cells can invade the healthy tissue surrounding the breast and spread to other parts of the body, a process called metastasis.

Unlike other cancers, breast cancer does not have an infectious cause. Instead, it results from a combination of genetic, environmental, and hormonal factors. Although the exact cause remains unclear, the following factors can increase one&#39;s risk: 
&nbsp;

<ul>
	<li>Gender:&nbsp;Women are at a higher risk of developing breast cancer. In Pakistan, 1 out of 9 women are at risk<a href="#accordion">[3]</a>. On the other hand, only 0.5-1% of the cases occur in men<a href="http://#accordion">[4]</a>. 
	&nbsp;</li>
	<li>Age:&nbsp;Increasing age (over 40 years) is associated with a greater risk of breast cancer. 
	&nbsp;</li>
	<li>Genetic:&nbsp;Although a family history of breast cancer increases one&#39;s risk, its absence does not mean that people are at a reduced risk. Moreover, certain gene mutations such as in the genes BRCA1, BRCA2, and PLAB-2 have been known to give rise to breast cancers. 1 in 4 cases of hereditary breast cancer and 1 in 5 cases of male breast cancer in Pakistan are a result of the BRCA1/2 mutation<a href="http://#accordion">[5]</a>.&nbsp; 
	&nbsp;</li>
	<li><a href="https://merisehat.pk/disease/obesity">Obesity</a>:&nbsp;Obese individuals are at a higher risk.&nbsp; 
	&nbsp;</li>
	<li>Reproductive Factors:&nbsp;Early menarche, late menopause, and nulliparity all increase one&#39;s risk of breast cancer.&nbsp; 
	&nbsp;</li>
	<li>Hormonal Factors:&nbsp;The use of oral contraceptives and postmenopausal hormone replacement therapy (HRT) puts women at an increased risk. However, discontinuation of contraceptive use can reduce the risk.&nbsp; 
	&nbsp;</li>
	<li>Environmental Risk Factors:&nbsp;Alcohol consumption, smoking, consuming processed food products, and radiation exposure can all increase one&#39;s chances of breast cancer. 
	&nbsp;</li>
	<li>Prior History:&nbsp;A history of breast cancer in one breast causes a 3- or 4-fold higher chance of a person developing cancer in the other breast<a href="#accordion">[6]</a>.&nbsp;</li>
</ul>

&nbsp;

However, even people without these factors can sometimes develop breast cancer. According to the World Health Organization (WHO), half of breast cancers develop in women without any risk factors other than gender and age<a href="http://#accordion">[4]</a>.&nbsp;

&nbsp;

Screening programs help detect breast cancer and reduce associated morbidity and mortality. The American Cancer Society (ACS) recommends annual screening mammograms for women aged 40 years and above. Moreover, women should conduct regular breast self-exams to get more familiar with their breasts and detect any changes, such as lumps, swelling, or skin changes. 
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Diagnosis

A breast examination is vital to diagnosing breast cancer in individuals. The doctor looks for lumps, swelling, signs of inflammation, nipple changes, skin changes, nipple discharge, or any skin tethering. Moreover, the doctor also looks for enlarged lymph nodes and lumps in the armpits.&nbsp;

&nbsp;

Other tests that help diagnose breast cancer include: 
&nbsp;

<ul>
	<li>Mammogram:&nbsp;Mammograms are often used to screen for breast cancer. It is a type of X-ray and helps detect abnormal growths or changes in the breast. In case of detection of any abnormality, doctors may conduct additional tests.&nbsp;</li>
	<li>Ultrasound:&nbsp;An ultrasound of the breast can help differentiate whether the lump is a benign cyst or a solid mass.&nbsp;</li>
	<li>MRI:&nbsp;MRI scans give a more detailed view of the structures of the breast and are often used as a screening tool for those at a higher risk of breast cancer.</li>
	<li>Biopsy:&nbsp;A biopsy is conducted if the doctor suspects cancer-based on the findings of the mammogram or ultrasound. It involves removing a small breast tissue sample and sending it to the lab for analysis. A biopsy is the only definitive way to diagnose breast cancer.&nbsp; 
	&nbsp;</li>
</ul>

<h5>Stages</h5>

As with other cancers, researchers stage breast cancer based on the size of the tumor and whether it has metastasized to the lymph nodes or other parts of the body. It helps doctors create an effective treatment plan for the patient.&nbsp;

The American Joint Committee on Cancer (AJCC)&nbsp;uses the TNM system to stage breast cancer<a href="#accordion">[7]</a>. It is based on the tumor size (T), whether the cancer has spread to the lymph nodes (N), and whether it has metastasized (M).&nbsp;

There are 5 main stages of breast cancer. These include:

&nbsp;

Stage 0:&nbsp;The disease is limited to the ducts and lobules of the breast and has not spread into the surrounding tissue. It is also called ductal carcinoma in situ (DCIS).&nbsp; 
&nbsp;

Stage I:&nbsp;This is an invasive stage characterized by cancer cells spreading to breast tissue. It has two types:

<ul>
	<li>Stage IA - The tumor is 2cm or less and has not infiltrated the lymph nodes</li>
	<li>Stage IB - Cancer spreads to nearby lymph nodes. There are either no cancer cells in the breast or the tumor is less than 2cm.</li>
</ul>

&nbsp;

Stage II:&nbsp;Invasive breast cancer has two types:&nbsp;

<ul>
	<li>Stage IIA - The tumor is either less than 2cm and has spread to 1-3 lymph nodes, or it&#39;s between 2-5cm and hasn&#39;t spread to the nodes.</li>
	<li>Stage IIB - The tumor is 2-5 cm and the disease has spread to 1-3 axillary lymph nodes. Or the tumor is larger than 5 cm&nbsp;but has not spread to the axillary lymph nodes.</li>
</ul>

&nbsp;

Stage III:&nbsp;There are three types:

<ul>
	<li>Stage IIIA - Tumor is either in the breast or in the lymph nodes. It has spread to more than 4 lymph nodes in the breast or axilla, but not other parts of the body.</li>
	<li>Stage IIIB - Tumor spreads to the chest wall causing swelling of the breast. It is also called locally advanced breast cancer. Moreover, cancer may have spread to up to 9 lymph nodes. Inflammatory breast cancer is considered Stage IIIB.</li>
	<li>Stage IIIC - Tumor has spread to 10 or more axillary lymph nodes, lymph nodes near the collar bone&nbsp;or near the breastbone.&nbsp;</li>
</ul>

&nbsp;

Stage IV:&nbsp;Also called metastatic breast cancer, cancer has now spread to other organs, such as the bones, brain, liver, lungs, distant lymph nodes, or chest wall. 
&nbsp;

A study conducted among Pakistani breast cancer patients found that, due to a lack of awareness, 89% of patients are diagnosed at a later stage while 59% are at an advanced stage<a href="#accordion">[8]</a>. 
&nbsp;

Treatment

Treatment is largely dependent on the stage of breast cancer, how much it has spread, and its size. While surgery is the most common option, doctors may often employ a combination of various treatments.

&nbsp;

Surgery: There are different types of surgery options depending on the person&#39;s tumor.

<ul>
	<li>Lumpectomy - The tumor and a small amount of surrounding healthy tissue are removed.</li>
	<li>Mastectomy - The entire breast is removed. And both breasts are removed in case of a double mastectomy. Some women may undergo a contralateral prophylactic mastectomy to lower their risk of developing breast cancer. Many women opt for breast reconstruction after their procedure. &nbsp;</li>
	<li>Sentinel Node Biopsy - It involves the removal of lymph nodes that the cancer cells drain to. If the doctor does not find cancer cells in the sentinel lymph nodes, then removal of other nodes is not necessary.&nbsp;</li>
	<li>Axillary Lymph Node Dissection - Axillary lymph nodes are removed if the cancer cells have spread to the sentinel lymph nodes. It helps prevent the spread of cancer.</li>
</ul>

&nbsp;

Chemotherapy: It destroys cancer cells and is often given after surgery, in combination with radiation. However, in some cases, chemotherapy may be given before surgery to reduce the tumor size.&nbsp;

&nbsp;

Radiotherapy: It is typically administered after lumpectomy and uses radiation to kill any remaining cancer cells.

&nbsp;

Hormone Therapy: Hormone-sensitive tumors are often administered hormone therapy. It helps lower the hormone levels; thus, they are unable to attach to the receptors and cause tumor growth.&nbsp;

&nbsp;

Other Medications: In some cases, doctors may also prescribe biological agents, such as Herceptin (trastuzumab), which blocks the body&#39;s production of HER2 proteins and slows cancer growth. Moreover, immunotherapy drugs are also often used in combination with chemotherapy. 
&nbsp;

The overall 5-year survival rate for breast cancer is 90%. However, these rates differ depending on the individual&#39;s type of cancer, its stage, age, and several other factors. Moreover, these are only estimates and cannot predict the success of the treatment option or how long the person will live after their diagnosis. 
&nbsp;

Key Points

<ul>
	<li>Breast cancer affects both men and women. It commonly begins as a painless lump and can be accompanied by breast swelling, nipple retraction, skin changes, and lymph node enlargement.&nbsp;</li>
	<li>Breast cancer can result from a combination of genetic, lifestyle, environmental, reproductive, and hormonal factors. In Pakistan, BRCA1/2 gene mutation accounts for 1 in 4 cases of hereditary breast cancer.</li>
	<li>Although mammograms can help screen for breast cancer, a biopsy is the only way to diagnose breast cancer. It can also help doctors stage the cancer and design a treatment plan for the individual.</li>
	<li>Common treatment options include chemotherapy, radiation, and surgery. 
	&nbsp;</li>
</ul>

[1] International Agency for Research on Cancer, 2021. World Cancer Day: Breast cancer overtakes lung cancer in terms of number of new cancer cases worldwide. IARC showcases key research projects to address breast cancer.

[2] International Agency for Research on Cancer, 2021. Pakistan Globocan 2020.

[3] Sohail, S. & Alam, S. N., 2007. Breast cancer in pakistan - awareness and early detection. Journal of the College of Physicians and Surgeons Pakistan, 17(12), pp. 711-2.

[4] WHO, 2021. Breast Cancer.

[5] Rashid, M. U. et al., 2019. Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study. Hereditary Cancer in Clinical Practice, 17(27).

[6] J Kollias, I. O. E. C. W. E. R. W. B., 1999. Clinical and histological predictors of contralateral breast cancer. European Journal of Surgical Oncology, 25(6).

[8] Gulzar, F. et al., 2019. Identifying the reasons for delayed presentation of Pakistani breast cancer patients at a tertiary care hospital. Cancer management and research, Volume 11, pp. 1087-1096.