Prognostic relevance of mixed histological subtypes in invasive breast carcinoma: a retrospective analysis

Purpose: The prognostic and therapeutic power of special histological subtypes in breast cancer in pure form or in combination with other histological subtypes is still not established, and diagnostic guidelines are cautious regarding prognostic power based on the histological subtype alone. Therapy decisions are guided in most cases independently of the histological subtype and are directed by biomarkers and tumor stage. In this study, we analyzed a comprehensive large retrospective breast cancer cohort with a special focus on histological subtype (other than ductal non-special type or lobular carcinoma) and correlated pure or mixed histological forms with pathological tumor stage and overall disease-free survival.

Materials and methods: A total of 827 breast cancer cases with pure or mixed special histological types were retrospectively analyzed. Survival information was available in 645 of 827 cases.

Results: A total of 293 cases had pure forms, and 534 cases had mixed histological subtypes. The most common pure special types were mucinous (23.9%), micropapillary (21.2%), high-grade metaplastic (13%), male breast cancer (8.2%), cribriform (6.8%), metastases (6.1%), apocrine and papillary (each 5.46%), NST with medullary and clear cell pattern (up to 3.4%) and high-grade neuroendocrine carcinomas (2.7%). Mixed forms were most frequently encountered in NST carcinomas with micropapillary components (41.8%), followed by mucinous (9.93%) and cribriform (6.74%) mixed patterns. In univariate analysis, no pure form had prognostic relevance compared with any mixed form with the basic pure element. Pooling pure histological subtypes with tumor stage and age in a linear random-effects model, the cribriform subtype had the most favorable prognosis, while male breast cancer showed the poorest outcome (p < 0.001). All other frequent pure forms had intermediate prognostic power (p < 0.001).

Conclusion: Our results show that the analyzed special histological breast cancer subtypes (other than ductal and lobular carcinomas) do not carry prognostic information alone, either in pure form or in any combination with other subtypes. Prognostic groups including special subtypes, however, can strongly stratify breast cancer if tumor stage, age and biomarkers are included in the prognostic measurements.