Diffuse Cutaneous Breast Cancer Metastases Resembling Subcutaneous Nodules With No Surface Changes

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Typically, cutaneous metastases of breast cancer manifests as a 1- to 3-cm, asymptomatic, firm, pink to red-brown nodule on the chest ipsilateral to the primary tumor. There may be more than 1 nodule, and ulceration may be present.^5,6 In addition to nodular metastases, which make up 47% of cases (N=305), other common presentations include alopecia neoplastica (12%), telangiectatic carcinoma (8%), melanomalike lesions (6%), carcinoma erysipeloides (6%), subungual lesions (5%), carcinoma en cuirasse (4%), and zosteriform metastases (4%).⁶

Although nodular metastases are the most common type of cutaneous breast cancer metastases, our case is unique in that the patient had soft nodules dispersed to both arms and legs, and the nodules had no surface changes. Although cutaneous metastases can present as flesh-colored nodules,⁷ they typically have an erythematous base, a slight change in coloration, or induration. Additionally, cutaneous metastases most often are few in number and appear in close proximity to the primary breast adenocarcinoma.⁸ Without the detection of a slight soft elevation on palpation, our patient’s nodules were practically indistinguishable from the normal skin.

Among common internal cancers, breast cancer is the most likely to metastasize to the skin at a rate of 2.42% per primary tumor (Table 1).¹ Cutaneous metastases from lobular carcinomas are much rarer than those from ductal carcinomas.⁴ The metastases also are most often located locally on the chest ipsilateral to the primary malignancy. Distant metastases are relatively rare. In a review of 212 cases of breast cancer patients with skin metastases, only 9 had involvement of the legs and only 4 had involvement of the contralateral chest.⁴ Our patient had involvement of the ipsilateral chest, both arms and legs, and the contralateral chest.

The 5-year relative survival rate for breast cancer patients varies based on the stage at diagnosis (99% in patients with localized cancer, 84% with regional lymph node involvement, 24% with distant metastases of any kind).⁹ In a study of 141 patients with cutaneous metastases in a Taiwanese medical center, Hu et al¹⁰ found that patients with breast cancer with only cutaneous metastases had a 5-year absolute survival rate of 38%. In the same study, patients with non–breast cancer metastasis including cutaneous metastasis had a 5-year survival rate of 15%.¹⁰ This data is summarized in Table 2.

Breast cancer metastasis to soft tissue (eg, the skin) typically indicates a better prognosis than breast cancer metastasis to a visceral organ or bone. In a study of 439 patients with metastatic relapse after surgical resection of a primary breast cancer, those who had soft tissue metastases had a median survival period of 39 months, whereas those who had visceral or bone metastases had a median survival period of 13 and 28 months, respectively.¹¹ Furthermore, cutaneous metastases from breast cancers do not necessarily indicate as poor a prognosis as skin metastases from other internal malignancies. Cutaneous metastases from other internal malignancies carry a relative risk of mortality of 4.3 compared to cutaneous metastases from breast cancer.¹⁰

Treatment of cutaneous metastases may be medically or cosmetically indicated. Standard treatments for cutaneous metastases from the breast include surgical excision, external beam radiotherapy, and systemic chemotherapy.⁶ While oncologists can use the response of cutaneous metastases to treatment as an indicator of systemic response to hormone therapy or chemotherapy,¹² the response may be poorer due to the skin’s relatively weaker blood supply.¹³

Our patient was first prescribed anastrozole, an AI. For metastatic hormone receptor–positive breast cancer, AIs are a first-line therapy in postmenopausal women. In one meta-analysis, AIs showed greater improvement of survival rates relative to other endocrine therapies such as tamoxifen, an estrogen receptor antagonist (hazard ratio of 0.87).¹⁴ After stopping anastrozole, the patient was prescribed fulvestrant, another estrogen receptor antagonist, along with a trial drug. In a randomized, double-blind, placebo-controlled trial, fulvestrant was found to be an effective second-line treatment after anastrozole for hormone receptor–positive breast cancer in postmenopausal women.¹⁵ Our patient was then started on everolimus, a chemotherapeutic agent, and exemestane, another AI. After first-line treatment with anastrozole, this regimen also has been found to be an effective second-line treatment with improved progression-free survival.¹⁶ For the bone metastases, our patient was treated with zoledronic acid, a bisphosphonate. In a meta-analysis, bisphosphonates were found to reduce skeletal-related complications by a median of 28% in breast cancer patients with bone metastases.¹⁷

Some promising new local treatments for cutaneous breast metastases include topical imiquimod and electrochemotherapy. In a small study of 10 patients whose malignancies were refractory to radiotherapy, imiquimod achieved a partial response in 20% (2/10) of patients.¹⁸ In another study, 12 patients received electrochemotherapy involving electroporation (applying an electrical field to increase cell membrane permeability and thus increase drug uptake) followed by local administration of bleomycin, an antineoplastic agent. Seventy-five percent (9/12) of the patients received a complete response with disappearance of the metastases.¹⁹

This case report provides a rare presentation of diffuse nodular cutaneous metastases of breast adenocarcinoma with no surface changes. The subtle clinical findings in our patient demonstrate the spectrum of clinical manifestations for cutaneous metastases. Our case also serves to highlight the need for close inspection of the skin, including palpation in patients with a history of internal malignancy.