One of the largest studies of its kind has suggested that histological type may be associated with a host of outcomes in breast cancer, – including overall survival, treatment response, and clinical course – despite patients’ triple-negative receptor status.

The cohort study of more than 8,000 individuals with rare breast cancers found that medullary carcinoma was the most common type, while metaplastic carcinoma had the worst five-year among the several rare histological breast cancer subtypes analyzed. 

Reporting online in JAMA Network Open, investigators from the Maroone Cancer Center at the Cleveland Clinic Florida in Weston, Florida explained that collectively, triple-negative breast cancers differ from those of other histological subtypes in that they demonstrate a more aggressive clinical course and earlier recurrence. 

“Although the literature and research on rare histological subtype breast cancer are sparse,” the authors wrote, “a more thorough understanding of the extent of the clinicopathological heterogeneity within this subtype may help to direct future research for treatment specificity.” As such, the goal of the investigation was to determine the clinical and demographic characteristics, treatment patterns, and overall survival for patients with histologically rare (<10% of breast cancers) triple-negative breast cancer types.

To help achieve these ends, the researchers turned to 2010-2016 data from the National Cancer Database. As part of the cohort study, they analyzed confirmed cases of medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast cancer. The study’s primary outcome was five-year overall survival, while secondary outcomes included the site of metastasis, effect of immunohistochemistry, management, and two-year mortality.

According to principal investigator Elizabeth B. Elimimian, MD, MPH, a total of 8,479 breast cancer patients (mean age 62.6 years; 99.5% women) were analyzed. Among these, it was found that metaplastic carcinoma was the most commonly diagnosed histological type, observed in 6,867 patients (81%). This was followed by adenoid cystic carcinoma, which affected 1,357 patients (16%). Only 255 individuals (3%) had medullary carcinoma. 

Nevertheless, medullary carcinoma presented earlier in life, at a median age of 53 years. By comparison, adenoid cystic carcinoma presented at 62 years and metaplastic carcinoma at 63 years. Not surprisingly, the proportion of tumors with triple-negative immunohistochemistry was found to vary according to histological type, and comprised 22.4% of medullary carcinoma patients (n=57), 48.1% of adenoid cystic carcinoma patients (n=653), and 53.0% of metaplastic carcinoma patients (n=3,637). 

The study also found that patients with adenoid cystic carcinoma were less likely to receive both radiotherapy (52.4%) and chemotherapy (12.9%) than were their counterparts with medullary carcinoma (radiotherapy 61.2%; chemotherapy 74.5%) and metaplastic carcinoma (radiotherapy 49.7%; chemotherapy 68.6%). 

Finally, the five-year overall survival rate was best for patients with medullary carcinoma (91.7%), followed by adenoid cystic carcinoma patients (88.4%). Individuals with metaplastic carcinoma, on the other hand, had the worst five-year overall survival rate, at 63.1%. Multivariable regression models revealed several factors associated with metaplastic carcinoma’s poor prognosis, including advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. 

The five-year mortality rate was 8.33% for adenoid cystic carcinoma, compared with 36.91% for metaplastic carcinoma.

These findings, the authors concluded, may help to positively impact the treatment of these patients. “Although histological subtyping of triple-negative breast cancer is not well established,” they wrote, “our analysis suggests heterogeneity in clinical presentation, histological profile, and IHC for these three rare breast cancers histological subtypes, which may be of prognostic and therapeutic importance.”

Future research focusing on rare subtypes of breast cancer is desirable, they added, and may help inform optimal management of these relatively understudied carcinomas.