Impact of breast cancer subtypes and patterns of metastasis on outcome

Abstract

Clinical outcome of patients with stage IV breast cancer is dependent on tumor biology, extent, and localization of metastases. Routine imaging diagnostics for distant metastasis is not recommended by the national guidelines for breast cancer follow-up. In this study, we evaluated different patterns of metastases of cancer subtypes in order to generate hypotheses on individualization of follow-up after breast cancer in the adjuvant setting. Patients of the Regional Breast Cancer Center Dresden diagnosed within the years 2006-2011 were classified into the five intrinsic subtypes luminal A (ER+, Her2-, G1/2), luminal B/Her2 negative (ER+, Her2-, G3), triple positive (ER+, PR+, Her2+), Her2-enriched (ER-, Her2+), and triple negative (ER-, PR-, Her2-) and with a median follow-up of 45 months. Tumor stage at time of first diagnosis of breast cancer as well as time and site of metastasis at first diagnosis of distant metastatic disease was analyzed. Tumor specimen of 2284 female patients with primary breast cancer was classified into five subtypes. Distant recurrence-free survival at 3 years was most unfavorable in Her2-enriched (66.8 %), triple negative (75.9 %), and triple-positive breast cancer (81.7 %). The same subtypes most frequently presented with visceral metastases only at first presentation: Her2-enriched 46.9 %, triple negative 45.5 %, and triple-positive breast cancer 37.5 %. Longest median survival of 2.3 years was seen in luminal A and in Her2-enriched metastatic disease, respectively. Median survival was significantly better in the luminal A, Her2-enriched, and triple-positive subtype compared to triple-negative breast cancer (p < 0.005). Differences in time to metastatic disease, first localization of metastases, and overall survival after diagnosis of metastatic disease were shown. Considering new targeted therapies and the option of surgery of oligometastases, screening for visceral metastases might be reasonable after diagnosis of Her2-positive subtypes.

The Prognostic Value of Luminal Subtypes of Breast Cancer and their Impact on the Patient's Outcome

“…It also observed that Her2-enriched subtype presented with primary and secondary metastatic disease in the same time, whereas triple negative breast cancer more likely developed metastatic disease as a secondary event, while the luminal A subtype cases with primary metastatic disease were diagnosed more frequently than cases with secondary metastases. (52) Similar results were reported by Sanpaolo P et al, Savci-Heijink CD et al and GarcíaFernández A et al (53)(54)(55) As regards to staging in our study, 9.75% of cases found to be as stage I, 34% as stage II, 40% as stage III and 16.25% as stage IV (p value=0.002). In a study by Jung HA et al, a total of 1145 patients were diagnosed with breast cancer and received curative surgery.…”

Intraocular Metastases Secondary to Breast Carcinoma Correlates With Upregulation of Estrogen and Progesterone Receptor Expression in the Primary Tumor

“…The resulting regulation of different signalling pathways and gene expression profiles influences the distinct biologic behavior of these tumor subtypes, including aggressiveness and organ-specific metastatic potential. [17][18][19][20] Expression of ER and PR receptors by choroidal metastases of BC and the consequently good response to hormonal therapy have been previously reported in single case reports. 3,15,16 Nevertheless, no work focusing on the ER, PR, and HER2 receptor expression in the primary tumor of patients affected by choroidal metastases of BC has been published, nor have there been any reports investigating the intraocular specific metastatic potential of different BC molecular subtypes.…”

“…Among all BC molecular subtypes, the skeleton was the most common site of metastatic disease, representing approximately half (48%) of patients, followed by liver (27%), lung (23%), central nervous system (17%), and pleura (7%). 20 Breast cancer subtypes differ not only in primary tumor characteristics, but also in their metastatic behavior. This fact could potentially be used in determining the appropriate strategy for patient follow-up.…”

“…The luminal A and B subtypes are associated with more bone metastases compared with the HER2-enriched and triple negative BC. 20 Furthermore, the luminal A subtype is associated with bone only metastases. Liver metastases are more frequently observed in HER2-enriched compared with luminal A and triple negative BC, and the luminal subtypes are less frequently associated with lung metastases compared with triple negative BC.…”

“…Liver metastases are more frequently observed in HER2-enriched compared with luminal A and triple negative BC, and the luminal subtypes are less frequently associated with lung metastases compared with triple negative BC. 20 The luminal A subtype is also less frequently associated with central nervous system metastases than HER2-enriched and triple negative BC. Similarly, the luminal B subtype is less frequently associated with central nervous system metastases compared with the HER2-enriched, showing a similar trend when compared with triple negative BC.…”