Breast Cancer Subtype Associated With Metastasis Pattern, Survival

Results of a recent retrospective study have shown that breast cancer subtypes are associated not only with patient survival but also with the pattern of distant metastases seen.

“This study demonstrates that subtypes of breast cancer mainly defined by ER [estrogen receptor], PR [progesterone receptor], and HER2 and are strongly related to the metastasis pattern, in terms of site-specific relapse, early/late metastasis, and survival outcomes,” wrote C. Dilara Savci-Heijink, of the Department of Pathology at the Academic Medical Center, Amsterdam, and colleagues in Breast Cancer Research and Treatment. “Hormone receptor-positive tumors have tendency to develop bone metastasis and they have better survival outcomes compared to hormone receptor-negative tumors with a tendency of developing visceral metastasis.”

Savci-Heijink and colleagues used tissue from 263 patients with metastatic breast cancer and stained the samples for ER, PR, HER2, EGFR (epidermal growth factor receptor), CK5/6, CK14, E-cadherin, TP53, and Ki67. Based on these results, the tumors were classified as ER-positive/HER2-negative/Ki67high, ER-positive/HER2-negative/Ki67low, ER-positive/HER2-positive, ER-negative/HER2-positive, and ER-negative/HER2-negative.

Patients developed distant metastasis by 30 months on average, with more than three-quarters of metastases developing within 5 years of treatment of the primary breast tumor. Data showed that women with hormone-negative disease developed distant metastases earlier than women with other subtypes (P = .003).

The median overall survival varied according to breast cancer subtype with the shortest survival in patients with ER-negative/HER2-negative tumors (27 months) and the longest survival in patients with ER-positive/HER2-negative/Ki67lower tumors (79 months). Patients with ER-negative/HER2-negative tumors had a median survival of 10 months after detection of distant metastasis compared with a median survival of 19 months in women with HER2-positive tumors (P = .020).  Longer survival was seen in women with ER-positive/HER2-negative tumors (25 months) and ER-positive/HER2-positive tumors (24 months).

Visceral metastasis was found in 76.8% of patients and was most common in women with ER-negative/HER2-negative tumors (81%).

More than 70% of metastases were bone metastases. Other common metastatic sites included the liver (54.5%) and the lung (31.4%). Again, the site of metastases varied by breast cancer tumor subtype. The lowest rate of bone metastases was seen in patients with ER-negative/HER2-negative tumors (55.2%). This rate increased for patients with HER2-positive tumors (69.8%), ER-positive/HER2-negative/Ki67high tumors (87.8%), and ER-positive/HER2-negative/Ki67low tumors (73.1%).

In their discussion of these results, the researchers pointed out that “further subgrouping of ER-positive/HER2-negative tumors according to their Ki67 status revealed that only a minority (6.3 %) of these tumors had low Ki67 status.”

“Within this group of tumors, there was also no significance regarding metastasis pattern. This result may suggest that if once metastatic event occurs, prognostic relevance of Ki67 might be limited,” they wrote.