Paget’s disease of the breast is among breast cancer symptoms along breast pain. Paget’s disease nipple and surrounding areola typically has a red, scaly rash.

Paget’s Disease Of The Breast

Online Consultation

Ismail Munir

Overview

Paget&rsquo;s disease is a less common type of breast cancer that usually involves the skin around the nipple. The darker skin around the nipple is called the areola and Paget&#39;s disease can also develop in it. Therefore, it is also called mammary Paget disease or Paget disease of the nipple.&nbsp;

Another tumor can also occur within the breast in patients with Paget disease. These internal breast tumors are usually invasive types or ductal carcinoma in situ, meaning cancer has not yet spread to other tissues. However, the presence of invasive breast cancer is linked to a poor prognosis. The most significant sign of Paget&rsquo;s disease is the Paget cells that take origin from the epidermis (the uppermost layer) of the skin of the areola and the nipple. These cells occur as single cells in the form of a group of cells and appear to be large and rounded under the microscope<a href="#accordion">[1]</a>. 
&nbsp;

The relationship between changes in the nipple and breast cancer was first identified by a British doctor named Sir James Paget in the 19th century. In 1874, he identified 15 females with nipple changes that later progressed to breast cancer.&nbsp;

The patients with Paget&rsquo;s disease had a significant lesion characterized by an eczematous and ulcerative appearance with the secretion of yellowish and clear exudate. At the beginning of the disease, these lesions seemed to be benign. However, later it was discovered that these ulcerative and eczematous lesions contained malignant cells that had the potential to affect the surrounding tissues. The fact that this disease affected the mammary glands supports the name mammary Paget disease.&nbsp;

Another similar disease was also discovered, in both males and females, which was associated with the external genitalia. Therefore, it was called extra-mammary Paget&rsquo;s disease.

The National Cancer Database (NCDB) in the United States analyzed the disease characteristics of 7,191 patients with Paget&rsquo;s disease of the breast. As per the results, the disease was most common in white people and only 2.1% of the patients were men. When comparing treatments, researchers noted a higher success with total mastectomy (65.3%) than with partial mastectomy (30.3%). Only 0.1% had to go through tumor destruction whereas 4.3% of them did not have to undergo any surgical removal or invasive procedure.

In a subset of 6,864 patients that had to go through surgical removal, complete mastectomy, or partial mastectomy, the 5-year survival rate was found to be 82.5%. The reason for the lower survival rate was age, ethnicity, metastasis of the tumor to the neighboring lymph nodes, metastasis, and a higher grade and stage of cancer. Survival rates and prognosis are also affected by the size of the tumor<a href="#accordion">[2]</a>.

There is epidemiological evidence that the incidence of Paget&rsquo;s disease of breast cancer is decreasing over time. It is not known why the incidence has decreased, but fortunately, it has decreased by 45% to that of the incidence rate in 1988-20223. Paget&rsquo;s disease associated with ductal carcinoma in situ has shown an even greater decline<a href="#accordion">[3]</a>.

Although Paget&rsquo;s disease has a characteristic appearance and secretion, it is important that anybody with a chronic skin rash go for a detailed medical evaluation.&nbsp; 
&nbsp;

Signs And Symptoms

Paget&#39;s disease of the breast is usually associated with one of the breasts, but in rare cases, it may involve both breasts. In the early stages, the symptoms may occur intermittently but as the disease progresses, the symptoms worsen and become persistent.

&nbsp;

Some of the common symptoms are given below<a href="#accordion">[1]</a>:

<ul>
	<li>Extreme drying, scaling, or flaking of skin surrounding the nipple</li>
	<li>Soreness of the nipple, associated with inflammation, redness, or warmth</li>
	<li>Frequent itching on the nipple that might be severe and lead to burning</li>
	<li>Weeping eczema-like lesions with oozing secretions and crusting</li>
	<li>A&nbsp;palpable breast lump&nbsp;</li>
	<li>Pus-like discharge or bleeding from the nipple in advanced stages</li>
	<li>Flat or inverted nipple&nbsp;</li>
</ul>

<div>&nbsp;</div>

Causes

The definite cause of Paget&#39;s disease is still unknown and is a mystery like any other cancer. However, scientists have come up with innovative techniques to help us become more aware of such processes.&nbsp;

The cells in our body are constantly undergoing replication so that the old cells are discarded and the newer cells become optimally functional. Cancer is a disease that is caused due to the abnormal growth of the cells in our body. However, this abnormal growth either leads to the formation of non-functional cells or an abundance of cells that causes pathology. This abnormal growth is due to the cellular changes that occur on the level of DNA or the genetic code. Even a minimal change in the DNA can lead to a totally different phenotype (visible attributes i.e. hair color) and, hence, these alterations may lead to the generation of cancer cells.

&nbsp;

The pathophysiology of this disease can be explained with the help of the following theories. Although many theories can lead to a better understanding of the disease, the most extensively accepted ones are given below<a href="#accordion">[3]</a>:

&nbsp;

<ul>
	<li>
	<h5>Epidermotropic&nbsp; Theory</h5>
	</li>
</ul>

Epidermotropic theory suggests that the origin of Paget&rsquo;s disease is an underlying mammary adenocarcinoma (tumor of a gland). The neoplastic ductal epithelial cells migrate through the ductal systems in the breast and reach the epidermis of the nipple, where they start colonizing. In this way, the neoplastic cells make a network or a mesh extending from the ducts to the epidermis.

&nbsp;

<ul>
	<li>
	<h5>Transformation&nbsp; Theory</h5>
	</li>
</ul>

According to the transformation theory, there is no relationship between the neoplastic cells of the ducts and the appearance of skin lesions. Rather it suggests that it&rsquo;s present as an epidermal carcinoma in situ that arises from the epidermal keratinocytes. In 1881, George Thin supported this theory with the reason that the secretions from the breast ducts damage the epithelium. The continuous damage leads to the transformation of the keratinocytes into cancer cells. Also, a small percentage of patients having Paget&rsquo;s disease of breast do not have an adenocarcinoma, which provides further weight to this theory.&nbsp;

There are always some risk factors associated with the development of cancer. It is commonly hypothesized that if the body is exposed to radiation, toxins, or other environmental hazards, it is more likely to develop cancer. For example, smokers have a higher risk of mouth cancer and lung cancer; similarly, alcohol consumers have a higher chance of developing liver cancer. However, in the case of breast cancer, it was seen that 85% of breast cancer occur in people with no risk factors<a href="#accordion">[1]</a>. 
&nbsp;

Self-examination for breasts is advised for every woman so that they can be aware of any problem early on. Breast self-exams are quite convenient and any woman can perform them on her own. It comprises some simple steps that have been elaborated on below<a href="#accordion">[5]</a>:

&nbsp;

<ul>
	<li>
	Step 1:&nbsp;Stand in front of a mirror with your hands on your hips and start looking at your breasts in the mirror with an erect posture. Observe closely to see any deformity or anything that looks abnormal to you. Check the symmetry, appearance, and color by paying close attention.
	</li>
	<li>
	Step 2:&nbsp;Raise your arms and examine the breast more closely. Check the mobility and appearance of the breast as you raise your arms.
	</li>
	<li>
	Step 3:&nbsp;While you are in front of the mirror, see if there&rsquo;s any fluid oozing out of your breast nipples. It may either be a clear fluid, yellowish fluid, pus, or watery secretion. Even if the secretion is milky or bloody, it is an alarming situation.
	</li>
	<li>
	Step 4:&nbsp;Lie down on your back and feel both breasts to check for any lumps, tenderness, pain or stiffness, etc.
	</li>
	<li>Step 5:&nbsp;Stand up and feel your breasts to see any abnormality. If there is some abnormality, or you find something suspicious then you must go to a doctor for an elaborate examination.</li>
</ul>

&nbsp;

If any of the above signs are positive, the doctor might have to investigate further and ask you the following questions<a href="#accordion">[6]</a>:

<ol>
	<li>What are your symptoms and for how long have you had them?</li>
	<li>Is there anyone in your family with breast cancer, or does cancer run in your family?</li>
	<li>Have you ever experienced eczema before or do you have any skin-related disease in the family?</li>
	<li>What is your age and are you menopausal (a physiological condition in which women stop having periods after the age of 40 or above)?</li>
	<li>Are you a regular alcohol consumer or do you consume alcohol at all?</li>
	<li>Have you gained weight recently and if yes, how much?</li>
	<li>Do you smoke, if yes, how much?</li>
	<li>Have you ever been on hormone replacement therapy or any medication to correct your hormones?</li>
	<li>Have you ever taken oral contraceptive pills?</li>
</ol>

The doctor may refer you to an oncologist if they suspect you have the disease. 
&nbsp;

Diagnosis

The diagnosis of Paget&rsquo;s disease can be confirmed only at a breast cancer clinic/hospital. At the clinic, they run the patient through a series of screening tests to confirm the diagnosis. When the diagnosis is confirmed then the grading, staging, and type of cancer need to be ascertained to formulate the treatment plan.&nbsp;

&nbsp;

The major tests include the following<a href="#accordion">[6]</a>:

&nbsp;

<ul>
	<li>
	<h5>Mammogram</h5>
	</li>
</ul>

For women aged 35 and over, a mammogram is a suitable procedure. It uses X-rays to create an image of the ducts and the glands in the breasts. A mammogram helps to figure out any early changes in the breast tissue that cannot be done with the naked eye or cannot be felt with hands. In younger women, it is more difficult to identify breast changes because younger women have more dense breasts. Therefore, this test is not for women younger than 35 years.

&nbsp;

<ul>
	<li>
	<h5>Ultrasound&nbsp; Scan</h5>
	</li>
</ul>

The first line of investigation for Paget&rsquo;s disease in young women is ultrasound scans. Young women have dense breasts which are not suitable for mammograms. Therefore, ultrasound is preferred. The ultrasound also helps the doctor to figure out if the lump in the breast is solid or liquid. Regular check-ups are recommended for females under the age of 35.

&nbsp;

<ul>
	<li>
	<h5>Skin&nbsp; Biopsy</h5>
	</li>
</ul>

If the doctor suspects that the patient has Paget&rsquo;s disease, the diagnosis is confirmed with the help of a skin biopsy. It is one of the terminal investigations because it confirms the disease. In this test, the doctor takes a tissue sample from the skin of the nipple and the area surrounding it. After extraction, this sample of the skin is examined under a microscope to see if the cells are normal or cancerous.

&nbsp;

<h5>Staging And Grading</h5>

Staging and grading of the disease are important as it helps your healthcare practitioner to choose a treatment regimen.

&nbsp;

The following are the widely accepted stages<a href="#accordion">[4]</a>:

<ul>
	<li>
	Stage&nbsp; 1 -&nbsp;&nbsp;Stage 1 breast cancer refers to cancer that is small and only in the breast tissue, or it might be found in lymph nodes close to the breast.
	</li>
	<li>
	Stage&nbsp; 2 -&nbsp;&nbsp;It is defined as cancer that is either in the breast, the adjacent lymph nodes, or both. It is early-stage breast cancer.
	</li>
	<li>
	Stage&nbsp; 3&nbsp;- Stage 3 has a unique characteristic of being spread from the breast to the close-by lymph nodes, the skin of the breast, or to the chest wall.
	</li>
	<li>
	Stage&nbsp; 4 -&nbsp;&nbsp;Lastly, stage 4 breast cancer can be defined as cancer that has spread to other parts of the body.
	</li>
</ul>

&nbsp;

The grades describe the appearance of the cancerous cells and consist of:

<ul>
	<li>
	Low&nbsp; Grade&nbsp; (G1) -&nbsp;&nbsp;The cells, although abnormal, are growing slowly.
	</li>
	<li>
	Medium&nbsp; Grade&nbsp; (G2) -&nbsp;&nbsp;The cells look more abnormal than the low-grade cells seen in G1.
	</li>
	<li>
	High&nbsp; Grade&nbsp; (G3) -&nbsp;&nbsp;The cells look more abnormal and are more prone to grow quickly.
	</li>
</ul>

<div>&nbsp;</div>

Treatment

Surgery is the ultimate treatment for Paget&#39;s disease. If the cancer is limited and is of a small size then only the tumor along with some of the surrounding tissue such as the nipple and the areola are removed.

However, if the cancer has spread to the surrounding tissue, it is necessary to remove the whole breast and this procedure is called mastectomy. There is always the possibility of pursuing breast reconstruction surgery post mastectomy. The aim of this surgery is to make a new breast after removal of the breast or part of the breast. It is important that the reconstructed breast matches the other one, however it is important to bear in mind that both breasts will not be identical.&nbsp;

If the tumor is invasive, and it&rsquo;s spreading to the other tissue and the lymph nodes, it is important that the patient be put on some medication along with the surgery.

&nbsp;

Some of the significant measures are<a href="#accordion">[7]</a>:

<ul>
	<li>Chemotherapy: It is a combination of powerful medicines that destroy cancerous cells. These medicines are always given in calculated doses to deal with the growth of tumor cells.&nbsp;</li>
	<li>Radiotherapy: In radiotherapy, controlled doses of high-dose radiation are allowed to pass through the cancerous growth. The highly replicating cells are targeted to destroy their genetic makeup and stop them from growing.</li>
	<li>Targeted Or Hormone Therapy: Hormone therapy or targeted therapy refers to the use of hormones that make the healthy tissue less susceptible to getting affected by cancer. Moreover, it also lowers the risk of cancer spreading to other parts of the body. 
	&nbsp;</li>
</ul>

If the cancer is detected and treated at an early stage, the prognosis is usually good. The potential complication with Paget&rsquo;s disease of the breast is that it is usually misdiagnosed and confused with some other disease which delays the treatment and subsequently, the cancer spreads in the surrounding tissue.

The treatment of Paget&rsquo;s disease of the breast leads to some temporary complications such as skin irritation, fatigue, pain, and indigestion, etc. As radiation, chemotherapy, and hormone treatments alter the growth of rapidly growing cells, they do have some negative impacts on the body as well. However, the advantages of the treatment outweigh the negative side effects by far, and often patients are prescribed medicines to help ease side effects (e.g. nausea, vomiting, etc.).

&nbsp;

&nbsp;Some of the long-term complications are<a href="#accordion">[8]</a>:

<ol>
	<li>Lymph node removal may lead to lymphedema.</li>
	<li>Chemotherapy or radiation therapy may increase the risk of other cancers.</li>
	<li>Hormone treatments and chemotherapy may lead to <a href="https://www.merisehat.pk/disease/infertility-in-men" target="_blank">infertility </a>or early <a href="https://www.merisehat.pk/disease/menopause" target="_blank">menopause</a>. 
	&nbsp;</li>
</ol>

Any risk factor that increases the risk of any other type of breast cancer also affects the risk of Paget&rsquo;s disease of the breast. Some of the major ones are mentioned below<a href="#accordion">[9]</a><a href="#accordion">[10]</a>:

&nbsp;

<ul>
	<li>
	<h5>Old&nbsp;Age</h5>
	</li>
</ul>

The risk of breast cancer increases with increasing age. It is more likely to be seen in women after the age of 40.

&nbsp;

<ul>
	<li>
	<h5>A&nbsp;Personal&nbsp;History&nbsp;Of&nbsp;Breast&nbsp;Conditions</h5>
	</li>
</ul>

If the patient has a history of atypical hyperplasia of the breast or lobular carcinoma in situ (LCIS), there is a chance that they might develop Paget&#39;s disease of the breast as well.

&nbsp;

<ul>
	<li>
	<h5>A Previous&nbsp;History&nbsp;Of&nbsp;<a href="https://www.merisehat.pk/disease/breast-cancer" target="_blank">Breast&nbsp;Cancer</a></h5>
	</li>
</ul>

Patients that have recovered from breast cancer in one breast still have a chance of developing breast cancer on the other side.

&nbsp;

<ul>
	<li>
	<h5>A&nbsp;Family&nbsp;History&nbsp;Of&nbsp;<a href="https://www.merisehat.pk/disease/breast-cancer" target="_blank">Breast&nbsp;Cancer</a></h5>
	</li>
</ul>

It is not necessary that all patients with Paget&rsquo;s disease of the breast must have some family member with a history of breast cancer. But for people that do have a relative, mother, or grandmother with breast cancer, they may have an increased chance of developing it themselves.

&nbsp;

<ul>
	<li>
	<h5>Inherited&nbsp;Genes</h5>
	</li>
</ul>

If the parents have any abnormality in their DNA, e.g. a well-known gene mutation in breast cancer, such as BRCA1 and BRCA2, it is more likely to be transferred to the children as well.

&nbsp;

<ul>
	<li>
	<h5>Radiation&nbsp;Exposure</h5>
	</li>
</ul>

Radiation exposure to the chest increases your chances of breast cancer.

&nbsp;

<ul>
	<li>
	<h5><a href="https://www.merisehat.pk/disease/obesity" target="_blank">Obesity</a></h5>
	</li>
</ul>

If a person is obese, they have an increased chance of Paget&#39;s disease.

&nbsp;

<ul>
	<li>
	<h5>Early Menarche&nbsp;</h5>
	</li>
</ul>

If a female starts her periods before 12 years of age, there&rsquo;s a high risk of Paget&rsquo;s disease as it increases the exposure of estrogen in her body.

&nbsp;

<ul>
	<li>
	<h5>Late&nbsp;<a href="https://www.merisehat.pk/disease/menopause" target="_blank">Menopause</a>&nbsp;</h5>
	</li>
</ul>

Women who begin menopause at an older age are at a higher risk of developing Paget&rsquo;s disease of the breast as it increases the exposure of estrogen in your body.

&nbsp;

<ul>
	<li>
	<h5>Never&nbsp;Been&nbsp;Pregnant</h5>
	</li>
</ul>

Women who have never been pregnant have a higher risk of developing Paget&rsquo;s disease of the breast.

&nbsp;

<ul>
	<li>
	<h5>Postmenopausal&nbsp;Hormone&nbsp;Therapy</h5>
	</li>
</ul>

Post-menopausal hormone therapy uses a combination of estrogen and progesterone to deal with the signs and symptoms of menopause. This therapy also increases the risk of Paget&rsquo;s disease of the breast.

&nbsp;

<ul>
	<li>
	<h5>Drinking&nbsp;Alcohol</h5>
	</li>
</ul>

Alcohol consumption is another reason for the development of breast cancer.

<div>&nbsp;</div>

Following are the factors that may help you prevent Paget&rsquo;s disease of the breast<a href="#accordion">[10]</a>:

&nbsp;

<ul>
	<li>
	<h5>&nbsp;Be&nbsp;Curious</h5>
	</li>
</ul>

Breast cancer has become a disease that is increasing at a very fast rate. It is important to screen and test yourself because it is highly curable if found at the initial stages. Ask your doctor when to start breast cancer screening exams and tests. General screening and testing include physical breast examinations and mammograms.

&nbsp;

<ul>
	<li>
	<h5>Do&nbsp;Regular Self-Examination&nbsp;Of&nbsp;Your&nbsp;Breast</h5>
	</li>
</ul>

By doing so, you become familiar with your breast structure and find any abnormality (if present) pretty soon. Learning self-examination is also important because we are all busy with our daily activities, leaving less time to visit a doctor. You can examine it at any time of the day or night at home and it will take only 5-10 minutes. Though breast awareness cannot prevent breast cancer, it can help you in understanding the minor changes that your breast undergoes and identify them when these signs and symptoms become unusual or aggressive. An early diagnosis leads to a better prognosis.&nbsp;

&nbsp;

<ul>
	<li>
	<h5>&nbsp;Quit&nbsp;Alcohol&nbsp;And&nbsp;Smoking</h5>
	</li>
</ul>

Tobacco and alcohol increase the risk of cancer due to their harmful effects. This risk increases substantially when both are performed together, hence it is best to quit both habits.&nbsp;

&nbsp;

<ul>
	<li>
	<h5>&nbsp;Exercise</h5>
	</li>
</ul>

It is a must and should be done most days of the week. We all know that a healthy body leads to a healthy mind and to keep your body healthy we all have to exercise daily. If you have a busy schedule and do not have a lot of time for exercise, go for a 20-30 minute walk every day. This itself can be enough for preventing diseases.

&nbsp;

<ul>
	<li>
	<h5>Limitation&nbsp;Of&nbsp;Postmenopausal&nbsp;Hormone&nbsp;Therapy</h5>
	</li>
</ul>

Taking a combination of hormone therapy can increase the risk of breast cancer, but since the risk of having breast cancer varies between individuals, it is best to discuss the dosage and duration of hormone therapy with your doctor.&nbsp;&nbsp;&nbsp;

&nbsp;

<ul>
	<li>
	<h5>&nbsp;Choose&nbsp;A&nbsp;Healthy&nbsp;Diet</h5>
	</li>
</ul>

Start following a Mediterranean diet which is composed of fresh fruits, legumes, vegetables, and grains cooked in virgin olive oil instead of butter or other oils. You can also have mixed nuts in your diet. Preferring fish over red meat can also decrease the risks of breast cancer. Remember a good diet contributes greatly to overall good health

<div>&nbsp;</div>

A total of 349 patients with active Paget&rsquo;s disease of the breast were part of a Phase 3 trial of zoledronic acid. The patients had a baseline alkaline phosphatase level of 427 U/L. However, zoledronic acid normalized the level of alkaline phosphatase in 89% of people in comparison to 58% of people in a comparison group randomly assigned risedronate. The other finding was that the quality of life scores was improved in the zoledronate groups in comparison to the risedronate ones.

To summarize recent studies have led to the widespread agreement for using a single shot of 5 mg intravenous injection of zoledronate also known as zoledronic acid as a first-line therapy for Paget&#39;s disease. Zoledronic acid is considered better owing to its superior action over other agents in biochemical remission and its unprecedented duration of maintenance of those remissions<a href="#accordion">[11]</a>.&nbsp; 
&nbsp;

Key Points

<ul>
	<li>Paget&rsquo;s disease is a rare type of breast cancer that usually involves the skin around the nipple.</li>
	<li>In a subset of 6864 patients who had to go through surgical removal, complete mastectomy, or partial mastectomy, the 5-year survival rate was found&nbsp;to be 82.5%.</li>
	<li>There is epidemiological evidence that the incidence of Paget&#39;s disease of the breast is decreasing over time. It has decreased by 45% to that of the incidence rate in 1988-2022.</li>
	<li>Signs and symptoms may include scaling and drying of the area around the nipple, eczematous lesion, and&nbsp;itching on the nipple.</li>
	<li>Screening tests include breast self-examination and regular checkups.</li>
	<li>The diagnosis of Paget&rsquo;s disease can be confirmed only at a breast cancer clinic with the help of either a mammogram, an ultrasound, or a skin biopsy.</li>
	<li>Surgery is the ultimate treatment for Paget&#39;s disease. If cancer has spread to the surrounding tissue, it is necessary to remove the whole breast and this procedure is called mastectomy</li>
	<li>Risk factors include higher age, early menarche, late menopause, previous history of breast cancer, and hormone replacement therapy.</li>
	<li>Recent studies have led to the widespread agreement for using a single shot of 5 mg intravenous injection of zoledronate also known as zoledronic acid as a first-line therapy for Paget&#39;s disease. 
	&nbsp;</li>
</ul>

[1] Paget's disease of the breast: Stages, symptoms & prognosis. Cleveland Clinic.

[2] Sisti A, Huayllani MT, Restrepo DJ, et al. Paget disease of the breast: A national retrospective analysis of the US population. Breast Dis. 2020;39(3-4):119-126. doi:10.3233/BD-200439

[3] Yasir M, Khan M, Lotfollahzadeh S. Mammary Paget Disease. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.