Adjuvant therapy boosts odds for patients with isolated tumor cells, micrometastases

SAN ANTONIO-Women with breast cancer who have isolated tumor cells or micrometastases in their sentinel lymph nodes are at increased risk for recurrence, even if their cancer otherwise has favorable features. Adjuvant systemic therapy, however, can attenuate that elevated risk, according to the findings of a major Dutch study.

"In the Netherlands, there is no consensus on the administration of adjuvant systemic therapy in patients who have metastatic deposits of 2 mm or smaller and otherwise favorable primary tumor characteristics," said Maaike de Boer, MD, lead investigator for the MIRROR study.

Currently, about half of such patients receive this therapy.

"This situation has given us the ultimate opportunity to evaluate the prognosis of small metastatic deposits in different cohorts of patients with and without the use of systemic therapy," she noted.

In the cohort study, the investigators used the Netherlands Cancer Registry to identify women who received a diagnosis of invasive breast cancer between 1997 and 2005, had favorable tumor characteristics (tumor size ≤1 cm, regardless of grade, or tumor size 1 to 3 cm combined with grade 1 to 2), and underwent a sentinel lymph node procedure, optionally followed by an axillary lymph node dissection (SABCS abstract 23).

Analyses focused on the women who, on the basis of the final N stage in central pathology review, met the following criteria:

• No involvement of the sentinel node;
   

• Isolated tumor cells in that node, defined as deposits measuring ≤0.2 mm; and
   

• Micrometastases in that node, defined as deposits measuring >0.2 to 2 mm

The presence of cancer cells in lymph nodes was assessed with H&E staining and, if that was negative, with immunohistochemistry, according to Dr. de Boer, who is an oncologist at the Maastricht University Medical Center.

In all, 838 women had no nodal involvement and did not receive any adjuvant systemic therapy, 832 had isolated tumor cells or micrometastases and did not receive any adjuvant systemic therapy, and 958 had isolated tumor cells or micrometastases and did receive adjuvant systemic therapy (hormonal therapy, chemotherapy, or both). Regardless of group, patients could also have undergone axillary radiation therapy.

In a first set of analyses looking at the prognostic impact of small metastatic deposits, the five-year rate of disease-free survival was significantly lower among the patients with isolated tumor cells or micrometastases who did not receive adjuvant systemic therapy than among the patients who did not have any nodal involvement, none of whom received adjuvant systemic therapy (76.7% versus 85.7%), Dr. de Boer reported. She noted that after stratification, the findings were essentially the same for patients with isolated tumor cells and for patients with micrometastases.

In a multivariate analysis that controlled for potential confounders (age, tumor size, grade, and hormone receptor status), patients with isolated tumor cells or micrometastases had a significant roughly 50% increase in the risk of recurrence or contralateral breast cancer relative to their counterparts without any nodal involvement (hazard ratio, 1.49). The magnitude of increased risk was similar for patients with isolated tumor cells (hazard ratio, 1.50) and patients with micrometastases (hazard ratio, 1.52) individually.

In a second set of analyses looking at the impact of adjuvant systemic therapy, the five-year rate of disease-free survival was significantly poorer among patients with isolated tumor cells or micrometastases who did not receive this therapy than among their counterparts who did (76.7% versus 86.3%). The findings were essentially the same for patients with isolated tumor cells and for patients with micrometastases after stratification.

In a multivariate analysis that controlled for potential confounders (age, tumor size, grade, and axillary treatment), patients with isolated tumor cells or micrometastases receiving adjuvant systemic therapy had a significant roughly 40% reduction in the risk of a recurrence or contralateral breast cancer compared with their counterparts not receiving this therapy (hazard ratio, 0.57). The magnitude of risk reduction was similar for patients with isolated tumor cells (hazard ratio, 0.67) and patients with micrometastases (hazard ratio, 0.50) individually.

Taken together, the study's findings "imply a pure prognostic impact of isolated tumor cells and micrometastasis," Dr. de Boer said. More remarkably, she added, the prognostic impact of the former was as large as that of the latter. "Our data show that both patients with isolated tumor cells and patients with micrometastases benefit from adjuvant systemic therapy," she concluded. Ongoing analyses will look at patterns of recurrence, she added.

Ongoing analyses will look at patterns of recurrence, she added. Dr. de Boer did not comment on the nature or origin of isolated tumor cells. Previous researchers have noted that, in some cases, isolated tumor cells may be benign epithelial cells that were dislodged during an earlier biopsy (JCO 24:1978-1979, 2006).