Paget’s disease of the breast is a rare form of breast cancer that starts with skin changes on the nipple and areola, often looking like a patch of eczema or dermatitis. Because the condition closely mimics common, harmless skin problems, it frequently goes undiagnosed for years while an underlying breast cancer grows undetected. First described by surgeon James Paget in 1874, the disease accounts for a small fraction of all breast cancers, yet its tendency to masquerade as something benign makes it one of the most commonly misdiagnosed.
What Paget’s Disease of the Breast Looks Like
The hallmark sign is an eczema-like change on the nipple. The skin becomes red, scaly, flaky, or crusty. Some people notice oozing or bleeding from the nipple, along with itching or a burning sensation. Over time, the nipple may flatten or invert. The affected area can thicken, and the skin changes may spread from the nipple onto the surrounding areola. A palpable lump in the breast accompanies the skin symptoms in some cases, but many people present with only the nipple changes and no mass they can feel.
The visual similarity to ordinary skin conditions is the central clinical problem. A systematic review of misdiagnosed cases found that melanoma was the most common wrong initial diagnosis, followed by atopic dermatitis, and the average delay from first symptoms to a correct diagnosis was about two and a half years.1PubMed Central. Dermatologic Mimickers of Paget’s Disease of the Breast: A Systematic Review The condition can also be mistaken for psoriasis or even basal cell carcinoma of the skin.2PubMed Central. Mammary Paget’s Disease Mimicking Benign and Malignant Dermatological Conditions: Clinical Challenges and Diagnostic Considerations A person who has been treating a “nipple rash” with steroid cream for months without improvement should consider asking for a biopsy.
The Connection to Underlying Breast Cancer
Paget’s disease of the nipple is not just a skin problem. In the vast majority of cases, there is a cancer deeper in the breast. One study found underlying carcinoma, either ductal carcinoma in situ (DCIS, a non-invasive form) or invasive ductal cancer, in 92% of patients with Paget’s disease, and this held even when no lump could be felt on examination.3PubMed. Underlying pathology in mammary Paget’s disease Other reviews put the association between Paget’s and intraductal cancer at 93 to 100%.4PubMed Central. Mammary and extramammary Paget’s disease The underlying cancer is also often multifocal, meaning it appears in more than one spot within the breast tissue.
This is why the skin changes should never be brushed off. A nipple rash that does not respond to standard dermatologic treatment within a few weeks warrants a punch biopsy of the nipple skin, which is the quickest way to confirm or rule out Paget’s disease.
How Paget’s Cells Get to the Nipple
Scientists have debated for over a century how cancer cells end up in the skin of the nipple. Two main theories compete. The epidermotropic theory says that cancer cells from a tumor deeper in the breast duct system migrate outward through the ducts and colonize the nipple’s surface layer. The in situ transformation theory proposes the opposite: that the malignant cells arise independently in the nipple skin, without migrating from elsewhere.5PubMed. Paget’s disease of the breast
The migration theory gets the most support because an underlying breast cancer is found so consistently. But the transformation theory has not been discarded entirely, because there are occasional patients where the underlying cancer sits far from the nipple, or where none can be found at all.6PubMed. Paget’s disease of the breast: a clinical perspective It is possible that both mechanisms occur in different patients, and the distinction matters clinically because it influences how aggressively the deeper breast tissue needs to be treated.
HER2 and the Molecular Profile
When pathologists examine Paget’s cells under the microscope, they look for molecular markers that help confirm the diagnosis and guide treatment. Three markers are especially useful: a protein called CK7, a transcription factor called GATA3, and a growth receptor called HER2. In one study, CK7 and GATA3 were each positive in 95% of Paget’s disease cases, and HER2 was overexpressed in 90%.7PubMed Central. Immunohistochemistry of mammary Paget’s disease. Cytokeratin 7, GATA3, and HER2 are sensitive markers CK7 positivity across all Paget’s cases was also confirmed in a separate study of 60 cases.8PubMed. Mammary and extramammary Paget’s disease: an immunohistochemical study of 83 cases
The HER2 finding has real treatment implications. Estimates suggest that anywhere from roughly 58% to 86% of Paget’s disease cases overexpress HER2.9PubMed Central. Significant efficacy of trastuzumab emtansine in HER2-positive relapsed mammary Paget’s disease: a case report and literature review That is a much higher rate than in breast cancer overall, where HER2 positivity runs around 15 to 20%. Because HER2-positive cancers can be treated with drugs that specifically target that receptor, this molecular profile opens up targeted therapy options that matter when the disease recurs or is advanced.
By contrast, estrogen and progesterone receptors, which are the targets for hormonal therapy in many breast cancers, are less commonly positive in Paget’s disease. One study found estrogen receptor positivity in only about 27% of Paget’s cases, and progesterone receptor positivity in none of the Paget’s cells themselves.10PubMed Central. Immunohistochemistry of mammary Paget’s disease. Cytokeratin 7, GATA3, and HER2 are sensitive markers This means that hormonal treatments like tamoxifen or aromatase inhibitors, which are a mainstay in many other breast cancers, are less often useful here.
Diagnosis and the Role of MRI
A punch biopsy of the nipple skin is the definitive test. If Paget’s cells are found, the next step is determining what lies deeper in the breast. Mammography is the standard starting point, but it misses underlying cancers in a meaningful proportion of cases, particularly when there is no palpable mass.
MRI has emerged as a valuable tool in this gap. In one study of patients whose mammograms were negative, MRI detected otherwise hidden disease in half of the patients scanned, and it accurately showed the extent of that disease in every case where cancer was found.11PubMed. MRI identifies otherwise occult disease in select patients with Paget disease of the nipple Other researchers have similarly found that MRI can reveal DCIS or invasive cancer in the breast tissue that neither mammography nor physical examination detected.12British Journal of Radiology. Usefulness of MRI in detecting occult breast cancer associated with Paget’s disease of the nipple–areolar complex This matters because knowing the exact location and extent of disease before surgery can change whether breast-conserving surgery is feasible or whether mastectomy is needed.
Surgery and Radiation
For decades, mastectomy was considered the default treatment for Paget’s disease. The reasoning was straightforward: the underlying cancer is so common and often multifocal that removing the entire breast seemed safest. That approach is still used, but breast-conserving surgery (removing the nipple-areola complex and surrounding tissue while preserving the rest of the breast) has increasingly been studied as an alternative, particularly when the underlying cancer is limited to DCIS rather than an invasive tumor.
The evidence on this is somewhat nuanced and depends heavily on what lies beneath the nipple changes. A meta-analysis found that local recurrence rates were much lower with mastectomy (about 6%) compared to breast-conserving surgery alone (about 21%), but adding radiation therapy to breast-conserving surgery brought the recurrence rate down significantly, to about 8%.13PubMed. Treatment of Mammary Paget Disease: A systematic review and meta-analysis of real-world data In other words, the combination of breast-conserving surgery with radiation can come close to matching mastectomy’s local control, though not quite.
The picture splits further when you separate patients by the type of underlying cancer. A systematic review found that for patients with Paget’s plus DCIS, breast-conserving surgery with radiation achieved survival outcomes that were actually better than mastectomy. But for patients with Paget’s plus invasive ductal cancer, the results flipped: breast-conserving surgery, even with radiation, showed higher local recurrence risk compared to mastectomy.14BJS. Oncologic outcomes after breast-conserving surgery with radiotherapy versus mastectomy in patients with Paget’s disease of the breast: systematic review and meta-analysis That said, another study using matched comparisons found no significant overall survival difference between the two surgical approaches for either group.15PubMed. Breast-Conserving Surgery in Patients With Mammary Paget’s Disease
When radiation is used alongside breast conservation, long-term outcomes look encouraging. One study with a median follow-up of over nine years found local control rates of 87% at both ten and fifteen years.16PubMed. Conservative management of Paget disease of the breast with radiotherapy: 10- and 15-year results These numbers are reassuring for patients who want to avoid mastectomy, though the decision ultimately depends on the extent and type of underlying disease, how well imaging can map it, and whether clear surgical margins can be achieved.
Sentinel Lymph Node Biopsy
Because an invasive cancer lurks beneath the Paget’s changes in a substantial number of patients, evaluating whether cancer has spread to the armpit lymph nodes is an important part of staging. A sentinel lymph node biopsy, where a surgeon removes the first one or two nodes that drain the breast and checks them for cancer cells, is now recommended in certain scenarios.
One study of patients with Paget’s disease alone (no obvious mass) found invasive cancer in 27% and positive sentinel lymph nodes in 11%, leading the researchers to recommend sentinel node biopsy in all Paget’s patients.17PubMed. The role of sentinel lymph node biopsy in Paget’s disease of the breast Other experts recommend sentinel node biopsy specifically when invasive disease is identified or when mastectomy is planned, since removing the whole breast eliminates the option for a later sentinel node procedure.18The American Journal of Surgery. Sentinel lymph node biopsy in Paget’s disease of the breast
Targeted Therapy for HER2-Positive Disease
Given that Paget’s disease overexpresses HER2 far more often than typical breast cancers, anti-HER2 drugs are an increasingly important part of the treatment landscape. These drugs include well-known agents such as trastuzumab, and newer antibody-drug conjugates like trastuzumab emtansine (T-DM1), which delivers a chemotherapy payload directly to HER2-positive cells.
A reported case of relapsed Paget’s disease that was HER2-positive showed successful regression of skin symptoms after treatment with T-DM1, and the broader literature supports the idea that HER2-positive Paget’s disease should be managed with the same anti-HER2 strategies used for HER2-positive breast cancer in general.19PubMed Central. Significant efficacy of trastuzumab emtansine in HER2-positive relapsed mammary Paget’s disease: a case report and literature review Because HER2 positivity is linked to a worse prognosis, incorporating targeted therapy when the molecular profile supports it can meaningfully change outcomes.
Prognosis and What Drives It
Outcomes in Paget’s disease vary widely depending on the nature of the underlying cancer. When the disease is limited to DCIS with no invasion, the prognosis is generally quite good with appropriate treatment. When invasive cancer is present, staging factors like tumor size and lymph node involvement become the main drivers of outlook, just as they would in any other invasive breast cancer.
One pattern that emerged from a population-based study is that patients who had both nipple skin changes and a palpable breast or armpit mass at the time of diagnosis faced a higher risk of recurrence than those who had either symptom alone.20PubMed Central. Prognostic significance of mammary Paget’s disease in Chinese women: a 10-year, population-based, matched cohort study This makes intuitive sense: the combination of skin involvement and a mass suggests more advanced disease. Early recognition of the nipple changes, before a lump develops, is the best route to catching the disease at a more treatable stage.
Paget’s Disease in Men
Men can develop Paget’s disease of the breast, though it is exceptionally uncommon. Male breast cancer itself accounts for less than half a percent of all breast cancers, and Paget’s disease of the nipple in men is rarer still.21PubMed Central. Paget’s Disease of Nipple in Male Breast with Cancer Because the condition is so rare in men, it tends to be diagnosed even later than in women. Men who notice persistent skin changes on the nipple, particularly redness, crusting, or ulceration, should seek evaluation rather than assume the change is harmless.
Treatment in men follows the same principles as in women. Modified radical mastectomy has been the most commonly reported approach in male cases, partly because the smaller volume of male breast tissue makes conservation less practical, and partly because the rarity of the condition means few centers have experience tailoring less aggressive approaches for men.
Extramammary Paget’s Disease
A related condition called extramammary Paget’s disease occurs in skin outside the breast, typically in areas rich in apocrine sweat glands: the vulva, the groin, the perianal region, the scrotum, and occasionally the armpits. Visually it can look similar, presenting as a red, scaly, well-defined plaque that grows slowly. Despite the shared name and some overlapping pathology, there are important differences.
Mammary Paget’s disease is almost always associated with an underlying breast carcinoma. Extramammary Paget’s disease, by contrast, is often a standalone skin process and is associated with an internal malignancy much less frequently.22PubMed. Mammary and extramammary Paget’s disease When extramammary Paget’s is linked to an internal cancer, it tends to be in organs near the affected skin, such as the bladder, colon, or cervix.23PubMed Central. Mammary and extramammary Paget’s disease Both mammary and extramammary forms share CK7 positivity on biopsy, which can help distinguish them from other skin conditions, but treatment strategies and prognosis differ enough that the two forms should be thought of as distinct diseases that happen to share a name.
Nipple-Sparing Mastectomy and Recurrence
Nipple-sparing mastectomy, which preserves the nipple-areola complex for cosmetic reasons during reconstruction, has become popular for many types of breast cancer. But for Paget’s disease, where the cancer directly involves the nipple skin, this approach carries a specific risk. A review of published cases found that recurrence after nipple-sparing mastectomy with implant reconstruction had an average latency of about 40 months, and the recurrent tumors were most often Paget’s disease with DCIS. The primary tumors in those recurrence cases were overwhelmingly HER2-positive and hormone-receptor-negative.24BioMed Central / World Journal of Surgical Oncology. Local recurrence of mammary Paget’s disease after nipple-sparing mastectomy and implant breast reconstruction: a case report and literature review This data is based on a small number of cases and should be interpreted with caution, but it underscores why most surgeons still recommend removing the nipple-areola complex when Paget’s disease is the diagnosis. Preserving the very tissue where the cancer has taken hold seems to invite local recurrence, and the wait-and-watch approach that might work for other breast cancers does not translate well here.