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Triple-Negative Breast Cancers Not All the Same

— Histology tied to treatment response, outcomes

Ƶ MedicalToday
A mammogram showing a large mass consistent with a breast cancer

Certain histological subtypes of triple-negative breast cancer (TNBC) were more aggressive with worse treatment response and clinical course compared with others, researchers reported.

A cohort study of 8,479 patients with rare breast cancers from the National Cancer Database between 2010 and 2016 indicated that metaplastic breast carcinomas had worse 5-year overall survival (OS) compared with two other rare TNBCs: medullary carcinoma and adenoid carcinoma. The 5-year OS rate for metaplastic carcinoma was 63.1% versus 91.7% for medullary and 88.4% for adenoid cystic carcinoma, according to Thomas A. Samuel, MD, of Cleveland Clinic Florida in Weston, and colleagues in .

The study appropriately interrogates the false monolithism of TNBC as a disease for which poor survival is universal, said Oluwadamilola "Lola" Fayanju, MD, MA, MPHS, of Duke University in Durham, North Carolina.

"Indeed, it appears that triple-negative adenoid cystic carcinomas have 5-year survival rates that rival hormone receptor-positive disease," Fayanju, who was not involved in the study, told Ƶ. "By examining outcomes among less common histological subtypes, the authors highlight the importance of more individualized investigation for 'orphan' breast cancers such as metaplastic carcinoma, for whom good outcomes -- particularly for triple-negative cases -- remain elusive."

Of the included patients (74.4% white), metaplastic carcinoma was the most common subtype (81%), followed by adenoid cystic carcinoma (16%) and medullary carcinoma (3%). Additionally, the proportion of tumors that were triple-negative varied for each subtype with the highest proportion in metaplastic carcinoma (53.0%), then adenoid cystic carcinoma (48.1%), and medullary carcinoma (22.4%).

Among patients with medullary carcinoma, having Medicare (HR 5.70, 95% CI 2.58-12.59) and stage III or stage IV disease (HR 6.48, 95% CI 1.87-22.37) were associated with adverse prognosis. The researchers also noted that chemotherapy was rarely given to patients with adenoid cystic carcinoma (12.9%).

For metaplastic disease, income, treatment, and metastatic site were all associated with adverse prognosis. Specifically, patients with an annual household income of less than $40,227 (HR 1.20, 95% CI 1.06-1.35) or from $50,354 to $63,333 (HR 1.17, 95% CI 1.04-1.32) had worse survival compared with patients with incomes of $63,333 or higher.

Not undergoing surgery at the primary tumor site (HR 1.64, 95% CI 1.38-1.94) and not receiving chemotherapy (HR 1.82, 95% CI 1.65-2.01) were also associated with worse survival, as was metastasis to the bone, liver, or the lung.

There were no factors associated with adverse prognosis that were unique to the adenoid cystic subtype.

The researchers noted that OS was best for patients with medullary carcinoma no matter the stage. In contrast, OS was lowest for metaplastic carcinoma regardless of stage.

"At stages III and IV, the likelihood of death for patients with adenoid cystic carcinoma was approximately two-thirds that of patients with metaplastic carcinomas; the mortality rate for patients with medullary carcinoma was approximately 24% of the rate death recorded for patients with metaplastic carcinomas," they wrote.

Study limitations included its retrospective nature, lack of data on tumor genomic profiles and levels of claudin and Ki-67 protein, "which helps control how fast cancer cells grow," the researchers explained.

Based on these results, Samuel and colleagues suggested that "heterogeneity in clinical presentation, histological profile, and IHC [immunohistochemistry] for these three rare breast cancers histological subtypes ... may be of prognostic and therapeutic importance."

  • Leah Lawrence is a freelance health writer and editor based in Delaware.

Disclosures

Samuel and co-authors, as well as Fayanju, disclosed no relevant relationships with industry.

Primary Source

JAMA Network Open

Elimimian EB, et al "Clinical and demographic factors, treatment patterns, and overall survival associated with rare triple-negative breast carcinomas in the US" JAMA Netw Open2021; DOI: 10.1001/jamanetworkopen.2021.4123.