A 55-year-old postmenopausal White woman in the US was diagnosed with ductal carcinoma in situ (DCIS) about 1 year ago. She has hypertension that is well-controlled on telmisartan. Family history is noncontributory with no history of breast disease. She presents to her oncologist today with a 2-month history of back pain at night and persistent unilateral nipple redness, soreness, and a serous, occasionally bloody discharge from the left breast. She describes intermittent burning and pruritus that have not improved with emollients or topical corticosteroids.
On examination, the left nipple appears erythematous with eczematous scaling, crusting, and superficial ulceration extending into the areola. The nipple is slightly flattened with early retraction, but no palpable breast masses or axillary lymphadenopathy are detected. A diagnostic mammogram shows post-surgical changes but no new masses or suspicious calcifications, while breast ultrasound reveals subtle thickening of the nipple-areolar complex without an underlying lesion. Concerned about the persistent skin changes, her oncologist performs a punch biopsy of the nipple, which reveals the presence of large, pale-staining cells with hyperchromatic nuclei scattered throughout the epidermis.
The patient’s presentation strongly suggests Paget disease of the breast, which is almost always associated with an underlying malignancy, most commonly DCIS or invasive ductal carcinoma (IDC). The characteristic eczema-like skin changes that fail to respond to topical steroids and the presence of Paget cells on biopsy confirm this diagnosis.
Eczema is typically bilateral and responds to topical steroids, unlike this case. Mammary duct ectasia can cause nipple discharge, retraction, and subareolar inflammation, but it is bilateral, lacks ulceration, and would not show Paget cells on biopsy. Contact dermatitis is also typically bilateral, triggered by irritants, and presents with itching, erythema, and vesicles rather than ulceration or discharge; it would improve with avoidance and topical steroids, to which this patient did not respond.
The patient undergoes an MRI of the chest, and it is found the patient’s tumor is poorly delineated which correlates clinically to not being palpable. Further imaging reveals metastases in the lumbar vertebrae that were biopsy-proven invasive breast metastases; full thickness core biopsies of the breast were also NAC-positive for Paget.
Determining the tumor’s ER/PR and HER2 expression is essential for guiding systemic treatment in metastatic breast cancer. This patient has biopsy-confirmed metastatic breast cancer with involvement of the lumbar vertebrae, making systemic therapy appropriate in this case. The choice of treatment depends on the molecular characteristics of the tumor.
SLNB and ALND are not appropriate in stage IV disease, where therapy takes precedence over nodal staging. SLNB is typically useful in early-stage breast cancer for staging but is unnecessary in metastatic disease, where distant spread already confirms advanced-stage cancer. Similarly, ALND is performed in node-positive early breast cancer but usually does not improve survival or influence systemic treatment in patients with metastatic disease. Genetic counseling is recommended by the NCCN as part of the initial workup, but only in patients who are at high risk for hereditary breast cancer; this patient’s family history is noncontributory and is therefore not needed.
Pathology results reveal the patient is ER/PR and HER2 positive.
This patient has confirmed bone metastases in her lumbar vertebrae which should also be addressed as part of her management. Before starting a RANKL inhibitor (eg, denosumab) or a bisphosphonate (eg, zoledronic acid, pamidronate) for bone metastases, a comprehensive dental examination is essential to assess for dental infections, poor dentition, or need for invasive dental procedures. These agents are associated with osteonecrosis of the jaw (ONJ), a serious complication often triggered by dental extractions or poor oral health. Identifying and addressing dental issues before initiating bone-modifying therapy significantly reduces the risk of ONJ.
While bone-modifying agents are essential for managing bone metastases, they should not be initiated before a dental evaluation due to the risk of ONJ. A mastectomy or lumpectomy is typically not performed on patients with metastatic breast cancer because current medical evidence shows that removing the primary tumor in this stage does not significantly improve overall survival and is considered largely palliative
The patient is cleared after her dental exam and proceeds with RANKL inhibitor (denosumab) treatment for her bone metastases.
Systemic therapy is the mainstay of treatment for metastatic disease, while HER2-targeted therapy is indicated if the tumor is HER2-positive, which is common in aggressive, high-grade tumors, like in this case. Therefore, initiating both therapies is most appropriate.
Radiation therapy with HER2-targeted therapy is usually insufficient as the primary treatment for metastatic disease, though radiation may be used for palliative purposes. HER2-targeted therapy alone is not adequate, as systemic therapy is needed to control disease progression. Systemic therapy alone is also suboptimal if the tumor is HER2-positive, as HER2-targeted therapy significantly improves survival and treatment response.
The patient starts systemic therapy with and experiences regression; she is tolerating therapy well. After approximately 8 months, a routine check-up reveals new metastases on imaging; however, no new lesions are identified in the brain.
Patients whose disease progresses on first-line therapy should be switched to another HER2-directed regimen, such as trastuzumab emtansine (T-DM1) or trastuzumab deruxtecan, in combination with appropriate systemic therapy; this approach has been shown to improve survival and disease control.
Discontinuing HER2-targeted therapy is inappropriate, as HER2-directed treatment remains essential in controlling HER2-positive metastatic disease and stopping it would lead to rapid progression. Using localized radiation therapy alone is insufficient, as it only provides palliative relief and does not address systemic disease spread. Opting for best supportive care is premature, as the patient is still tolerating treatment well and has effective systemic options available.
Editor's Note: Skill Checkups are wholly fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
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